Month: December 2018

Fixed-dose combination (FDC) Drugs & its Ban in India

What is Fixed-dose combination (FDC) Drugs :

Fixed-dose combination (FDC) that includes two or more active pharmaceutical ingredients (APIs) combined in a single dosage form, which is manufactured and distributed in fixed doses & are in the spotlight currently due to government’s ban on them.

According to US healthcare provider IMS Health, almost half the drugs sold in India in 2014 were FDC, making it a world leader in combination drugs.

What is the logic behind FDC drugs :

The logic behind FDCs is to improve adherence, simplify therapy and/or to maximise benefit for the patient courtesy the added effects of the multiple medicinal products given together. The common drugs that will be affected by the ban are Saridon and D-cold total. The ministry of Health and Family Welfare has prohibited the manufacture for sale, sale or distribution for human use of 328 Fixed Dose Combinations (FDCs) with immediate effect. It has also restricted the manufacture, sale or distribution of six FDCs subject to certain conditions.

 A government document titled ‘Policy Guidelines for Approval of Fixed Dose Combinations in India’, released in June 2013 had claimed that “FDCs have shown to be particularly useful in the treatment of infectious diseases like HIV, malaria and tuberculosis where giving multiple antimicrobial agents is the norm. FDCs are also of use in chronic conditions especially when multiple disorders often co-exist.”

For instance, several FDCs pack a combination of nimesulide and paracetamol and are sold under different brand names as an anti-pyretic, or medications to control fever. India reportedly boasts around 2,000 FDCs, four times more that what’s available in the US.

What makes FDC drugs Popular :

The one-word answer is cost. Instead of buying two, or more, separate medicines, a patient can buy just one FDC medicine to treat multiple illness symptoms, which typically works out easier on the wallet. Pharma companies, meanwhile, love them because it is far cheaper and quicker to combine existing active ingredients to make new products than to discover new medicines and manufacture them separately.

FDCs’ popularity in India is due to the reasons such as increased efficacy, better compliance, reduced cost and simpler logistics of distribution. FDCs have shown to be particularly useful in the treatment of infectious diseases like HIV, malaria and tuberculosis, where giving multiple antimicrobial agents is the norm. FDCs are also useful for chronic conditions especially, when multiple disorders co-exist.

Why Government banned FDC drugs :

The health ministry took this decision after the Drugs Technical Advisory Board recommended that “there is no therapeutic justification” for the ingredients contained in the banned FDC drugs and that these medicines “may involve risk to human beings”.

Health experts have long maintained that many FDC combinations in the market neither boast any advantage over individual drugs nor are safe. Simple logic dictates that chances of adverse drug effects and drug interactions can go up if medicines are combined instead of being taken separately. Apart from the fact that some of the drugs reportedly boast dangerous side-effects, unnecessary use of combination drugs makes the human body resistant to treatment.

Worryingly, published studies have long claimed that FDCs are often prescribed to cover up for diagnostic imprecision-likely making them extremely popular with quack doctors.

Hence, in a bid to stop the irrational use of FDCs, the Union Health Ministry on Wednesday banned the manufacture, sale or distribution of 328 varieties of FDC drugs for human consumption. The move will likely affect over 6,000 medicine brands.

“The banned FDCs account for about Rs 2,500 crore and represent only the tip of the iceberg. In our estimate, the market for unsafe, problematic FDCs in India is at least one-fourth of the total pharma market which is valued at Rs 1.3 trillion,” the All India Drug Action Network, a civil society group working on safety and access to medicines and one of the petitioners in the Supreme Court case, said in a statement.

Disadvantages of  FDC drugs :

FDC could be unsafe for consumption with potential health risk since the side effects of the combined product in FDC are different from those of its ingredients.

Sometimes the combination can come with risk that are not originally existed in the individual ingredients.

When an adverse reaction happens in a patient it is very difficult to identify which ingredients caused the reaction.

Many studies have pointed out that many of these combinations don’t have any advantages over individual drugs.

FDCs are famous, not because of its therapeutical effect, but because of the profits that are earned by the pharmaceutical companies due to the low production cost and high demand.

Why Government has not banned FDC drugs earlier :

To be sure, the latest ban on FDCs isn’t the first one. In 2007, the government ordered states to withdraw 294 combinations that were in the market without the approval of the central government. Drug companies and industry associations used legal means to push back the government’s order

Actually the health ministry has been gunning for “irrational” and “unsafe” FDCs for over two years now. In March 2016, the government had banned 344 FDCs, adding five more to the list subsequently, following a report submitted by the Prof CK Kokate committee.

But drug makers, including Pfizer, Procter & Gamble, Abbott, Glenmark, Sanofi, Wockhardt, Cipla, Lupin and Dr Reddy’s, had immediately moved various courts against the decision. The Delhi High Court alone had received over 450 petitions seeking a stay on the ban.

In December 2016, the Delhi High Court squashed the Centre’s decision, noting that it had acted on the advice of a ‘technical committee’, instead of consulting the Drugs Technical Advisory Board (DTAB) or the Drugs Consultative Committee. According to the bench, this violated the provisions of the Drugs and Cosmetics Act.

The health ministry had challenged this ruling in Supreme Court and, in December 2017, the latter directed DTAB to decide the fate of these FDCs.

Incidentally, the DTAB (Drugs Technical Advisory Board) has recommended restricted manufacture and sale of six other FDCs, subject to certain conditions based on their therapeutic justification. The SC also ruled that the government could not use the DTAB report to prohibit 15 of the 344 drugs in the original list as these have been manufactured in India since before 1988.

According to The Times of India, this exception covers several popular cough syrups, painkillers and cold medication with sales amounting to over Rs 740 crore annually. However, the apex court told the ministry that it is free to initiate a fresh investigation into the safety of these 15 drugs if it wants them banned.

How Pharma sector get affected by FDC drug ban :

The proposed government ban on over 340 combination medicine (fixed-dose combinations, or FDCs) will impact over 2 per cent  nearly Rs 2,900 crore  of the organised retail market, with popular cough syrups, painkillers and flu medicines like Phensedyl, Saridon, Sumocold, and Vicks Action 500  facing action. 

Large pharma companies have reportedly said that the impact is expected to be negligible since the FDCs in question are less than 2% of the pie. They added that over the last couple of years, they have either phased out such drugs or changed the combination.

Good Distribution Practices (GDP) in Pharmaceutical Products

Good distribution practice (GDP) is a quality warranty system, which includes requirements for purchase, receiving, storage and export of drugs intended for human consumption.

Good Distribution Practice (GDP) refers to the regulatory guidelines governing the wholesale distribution of medicinal products to ensure their quality and integrity is maintained throughout the supply chain from the manufacturer to the end user.

As part of this, the Drugs Controller General India (DCGI) has come out with draft guidelines on ‘Good Distribution Practices’ (GDP) for pharmaceutical products. The 54th Drugs Consultations Committee meeting in end-July had suggested, taking necessary provisions to impart legal sanctity to the suggested guidelines in the rule book Drugs and Cosmetics Rules 1945, to penalise the offenders. The DCGI has asked all related stakeholders to respond to the draft guidelines to finalise the legislation.

On September 25, 2018, the Central Drugs Standard Control Organization (CDSCO) has released the draft guidelines on ‘Good Distribution Practices’ (GDP) to regulate the quality of pharmaceutical products over entire chain of distribution in the country.

The idea of GDP was initially deliberated in the 54th Drug Consultative Meeting held on July 07, 2018, and it was recommended to take necessary provisions to impart legal sanctity to the ‘GDP Guidelines’ as a Schedule to the Drug & Cosmetics Rules, 1945 (the ‘Rules’) to penalize the offenders.

According to a recent World Health Organization (WHO) report, an estimated 01 in 10 medical products circulating in low- and middle-income countries like India, is either substandard or falsified. According to the UN agency, these medicines not only fail to treat or prevent diseases but can also cause serious illnesses or even death. Further, the first-ever national drug survey 2014-16, conducted by the union Ministry of Health and Family Welfare, shows that over 3% of all drugs sold across India are of substandard quality.

At present transportation of drugs are carried out by third parties like contractors and sub-contractors in most cases. Contamination, cross contamination, mix-ups, adulteration and presence of spurious drugs are an issue in the unregulated distribution chain. Involvement of unauthorised entities in the distribution chain is also a concern.

The guidelines are to ensure the quality and identity of pharmaceutical products during all aspects of the distribution process. These include procurement, purchasing, storage distribution, transportation, documentation and record keeping practices in the chain from the manufacturing plant to the medical stores.

Objective of  these draft guidelines :

The objective of these draft guidelines is to ensure the quality and identity of pharmaceutical products during all aspects of the distribution process. These aspects include, but are not limited to procurement, purchase, storage, distribution, transportation, documentation and record-keeping practices. These guidelines are intended to be applicable to all persons and outlets involved in trade and distribution of pharmaceuticals, including the manufacturers of bulk, finished products, wholesalers, as well as others such as suppliers, distributors, Government institutions, international procurement organizations, donor agencies and certifying bodies, logistics providers, traders, transport companies and forwarding agents and their employees as well as health workers. It also covers biological products in general.

Documentation and records :

The guidelines lay out various measures to guarantee that medicines entering the distribution chain have proper documentation to permit tractability. Records of expiry dates and batch numbers should be part of the documentation to facilitate product recall. Moreover, procedures for procurement and release shall be in place to ensure that appropriate products are sourced only from approved suppliers and distributed by recognised entities. Inspection, auditing and certification of compliance with a quality system such as the ISO series or national guidelines by external bodies are recommended.

Storage and transportation :

The guideline suggests that the storage and transportation of pharmaceutical products should match the storage conditions indicated on the packaging/labelling information. The individuals responsible for the transportation of pharmaceutical products shall be informed about all relevant conditions for storage and transportation and these requirements shall be adhered to throughout the transportation and at any intermediate storage stages.

The entire storage facility should be temperature mapped under representative conditions. Equipment used for monitoring of storage conditions shall also be calibrated at defined intervals. Where special conditions are required during transportation that are different from or limit the given environmental conditions (e.g. temperature and humidity), these shall be provided by the manufacturer on the labels and shall be monitored and recorded. If a deviation has occurred during transportation, it shall be reported to the distributor and recipient of the affected pharmaceutical products.

Recalls and Returns :

The guideline envisages there shall be a system of written procedure for the management of recalls of defective pharmaceutical products with a designated person responsible for recalls. The system of recall shall comply with Drugs & Cosmetics Act, 1940 and Rules there under.

Recall operations shall be capable of being initiated promptly and at any time. The distributor shall follow the instructions of a recall message, the distribution records shall be readily available to the person(s) responsible for the recall and shall contain sufficient information on distributors and directly supplied customers (with addresses, phone and/or fax numbers inside and outside working hours, batches and quantities delivered). Recalled pharmaceutical products shall be identified and stored separately in a secure area while awaiting a decision on their disposal.


Note : The Draft GDP Guidelines for Pharmaceutical Products is available on CDSCO official website and is open for stakeholder comments/feedback, further for consideration and finalization of said Guidelines.

The same is mention in WHO good distribution practices for pharmaceutical products (Annex 5)
WHO Technical Report Series, No. 957, 2010.

What is FMD (Falsified Medicines Directive) in pharmaceuticals Packing

The FMD (Falsified Medicines Directive) is a legal framework introduced by the European Commission to improve the protection of Public health within the European Union. The directive applies since 2 January 2013 & the European Commission Delegated Regulation, (EU) 2016/161, supplements Directive 2001/83/EC with rules regarding safety features for the packaging of medicinal products for human use. The regulation was adopted in October 2015 to counteract to fake medicines include stricter record-keeping of wholesale distributors, pharmaceutical producers, an EU-wide quality mark to identify online pharmacies and mandatory safety features on packages.

It requires that a unique identifier must be encoded in a two-dimensional barcode printed on each unit of sale package which is to contain:

  • Product code
  • Randomized serial number
  • Expiration date
  • Batch or lot number
  • National Health Reimbursement Number if required

There must be a Tamper Evident Device.

When the medicine or vaccine is dispensed it must be scanned and the barcode decommissioned, so that it cannot be reused on a falsified medicine.

2,291 pharmaceutical companies with marketing authorizations to supply prescription medicines to the European Economic area are required to connect to the EU Hub established by the  European medicines verification Organization and upload the unique identifier for each pack of medicine they manufacture or repackage before February 2019. By August 2018 only 841 companies had completed the first stage of connection, which may take up to six months.

Around 1,500 pharmaceutical companies are at risk of failure to comply with the Falsified Medicines Directive (FMD) because they have yet to start working with the European Medicines Verification Organization (EMVO), the body has warned.

The FMD and its track and trace model :

The FMD introduces stringent regulations aimed to improve public health with new harmonized, pan-European measures that control and monitor the trade pathway of medicines to safeguard them for human use. The FMD track and trace regulations include multiple, diverse rules for all stages of the product, distribution and dispensation lifecycle, which derive from a strong foundation of safety feature regulations and rigorous verifications.

Fundamentally, the FMD enables a point of dispense verification model for medicines. To enable this model, the law requires the implementation of several different track and trace capabilities. There are three core regulations

1: Serialization :

The FMD requires serialization at the saleable pack or secondary level. For each pack of drug product, a unique serial number, coupled with the manufacturer product code, batch number and expiration date, are to be encoded in both a GS1 2D datamatrix and in human-readable form. A fifth data element, such as a national reimbursement number, may be required based on country requirements.

2: Compliance reporting :

The Marketing Authorization Holder (MAH) has several reporting and notification requirements under the FMD. The primary regulations apply to product master data and serialized product pack data. First, master data about the product, including product codes, form, strength, doses per pack, pack type, and target market(s) for distribution, must be reported to the European hub for each unique product form produced along with any subsequent updates. Serialized product pack data must also be reported, including product codes, lot/batch number, expiry data and serial numbers, for each unit of drug product shipped into the supply chain. Drug product status must also be maintained and updates made to the EU hub. These status updates may be required at a batch level if a recall is initiated, or at a saleable unit level in situations such as the decommissioning of serial numbers due to destruction of drug product.

3: Verification and safety features :

The FMD requires verification of the safety features, including the serialized product identifier, at least once before the product leaves the supply chain and is dispensed to the patient. The drug package barcode is scanned, and the information is submitted in a query to a national repository system which contains data about the drug package that was originally submitted by the manufacturer or marketing authorization holder. The national repository checks to verify that the product code and serial number of the product scanned matches an active unique identifier in the system. Under simple distribution when the product moves from MAH to wholesaler to pharmacy, this verification is performed by the pharmacy dispenser.

Simple in concept, complex in implementation :

The FMD creates an umbrella harmonized regulation covering the member states of the EU, plus four other countries (Norway, Iceland, Liechtenstein and Switzerland). The law also provides flexibility in how the regulations apply for drug products targeted for dispensation within a given country. So, a pharmaceutical company preparing for FMD regulations needs to design their serialization and compliance infrastructure both for the extreme scalability challenges presented by the FMD and the flexibility required to serve the member states. For example, a drug product may be regulated as a prescription medicine in one member state but not another, thereby creating serialization requirements for some drug packages and not others.

Certain prescription drug products may be white-listed, or exempted, from the safety feature requirements. A member state may follow the standard GS1 GTIN to identify the drug product, or they may require a unique national product code to be used. Member states may also require additional data to be captured, stored and reported with each drug product, such as a national reimbursement number. These are some of the complexities facing a pharmaceutical company preparing their internal packaging sites and external CMO network, and the CMO looking to serve a diverse pharma client base when preparing for FMD compliance.

Managing the network becoming bigger challenges :

Implementing a secure compliance infrastructure for EU FMD means that pharmaceutical companies and their supply network partners are challenged with mastering a never-before-seen level of network management .

European citizens are entitled to medicines that are safe, of high quality and effective. Falsified medicines may contain ingredients of low quality or in the wrong dosage – either too high or too low – and therefore pose a major health threat to EU citizens. The Falsified medicines Directive– which entered into force on 2 January 2013 – makes medicines safer by providing measures to verify their authenticity and improve the quality of their ingredients. The main novelties are three:

  • First, prescription medicines will need to bear, on their outer packaging, a pack-specific number and an anti-tampering device that will allow the pharmacist to verify that the medicine is authentic and unopened before dispensing it. This will prevent falsified medicines from reaching the patients.
  • Second, the active ingredients of medicines are to be manufactured according to appropriate quality standards (“good manufacturing practice for active substances”) regardless of whether they are manufactured in the EU or imported. If imported, the country of origin has to certify that the active ingredient has been manufactured according to standards equivalent to those of the Union. These provisions ensure that only safe, high quality ingredients are used in medicines in the EU. 
  • Third, legitimate online pharmacies will be identified by the same logo across the EU. The logo, when clicked, will allow the verification of the legitimacy of the pharmacy. This will allow EU citizens to make an informed choice when buying medicines over the internet. 

The Falsified Medicines directive marks a real breakthrough for the safety and quality of medicines circulating in the EU, not only it will be more difficult for falsified medicines to reach patients, but also European citizens will be able to buy medicines online through verified sources. Furthermore the Directive will also ensure the use of only high quality of ingredients in the composition medicines that have a beneficial effect on the level of public health protection in the EU.

Fake medicines entering the legitimate medicines supply chain is a growing problem. Such occurrences are difficult to detect but, according the Medicines and Healthcare products Regulatory Agency, since 2004 there have been nine known cases of fake prescription-only medicines reaching patients through the legal supply chain in the UK.

To tackle this problem the EU adopted Directive 2011/62/EU, known as the “Falsified Medicines Directive”, in July 2011. The Directive aims to prevent falsified medicines entering the supply chain and reaching patients by strengthening all aspects of the manufacture and supply chain across Europe. It introduces increased regulatory requirements for suppliers, manufacturers and wholesalers.

What is a unique identifier?

Medicines packaging will have to contain a unique identifier so that prescription medicines can be verified, and individual packs can be tracked through the supply chain. The European Commission is currently consulting on a concept paper about the technical specifications of this unique identifier, and is considering three options: a traditional linear barcode, a two-dimensional (2D) matrix barcode and radiofrequency identification (RFID). A limitation of linear barcodes is that they are unable to carry large amounts of information. 2D matrix barcodes can hold much more data but, currently, many pharmacies in Europe including in the UK  are not equipped with the scanners required to read them.

An RFID (Radio-Frequency Identification) An RFID (Radio-Frequency Identification) are a type of tracking system that uses smart barcodes in order to identify items. These radio waves transmit data from the tag to a reader, which then transmits the information to an RFID computer program.

How will this work?

It is proposed that the serial numbers (contained in the unique identifiers) for all medicines will be checked in to a data repository by manufacturers and then, at the point of dispensing, a pharmacist will scan each unique identifier and check out the medicine being dispensed.

What will need to be authenticated?

Not all medicines will require a unique identifier. The Directive states that all prescription medicines will need to be authenticated, unless they are included in a “white list” of medicines that are deemed not to be at risk of falsification. Conversely, medicines that do not require a prescription will not need a unique identifier unless they are put on a “black list”, in which case they will need to be authenticated before supply. Details about how the black and white lists will be compiled are part of the consultation process and, consequently, are not yet known.

How FMD Works & its Features :

How FMD Works


FMD Safety Features

How medicines verification will work in practice :

Manufacturers will give all their packs unique serial numbers and packs will carry a code that includes what the product is, the serial number, batch and expiry data. Depending on the market, there may also be a reimbursement number, although this is not relevant in the UK. This will all be encoded in a 2D barcode or matrix printed on each pack.

Manufacturers will upload this pack data to the European Medicines Verification System (EMVS), a central information hub and data router. As medicines are shipped to their point of sale, such as the UK, data from the EMVS will be transferred to the UK’s National Medicines Verification System (NMVS).

The FMD applies to prescription-only medicines as well as some over-the-counter medicines where there is a track record of counterfeiting. The package will be tracked from manufacturer through to the pharmacy, where it will be dispensed to the patient.

The pharmacist will scan the code on the pack and send the data to the NMVS (National Medicines Verification System) & In the vast majority of cases, this should return a message saying that the code matches one uploaded by a manufacturer and the pack is genuine. The pharmacist will then decommission the pack  changing its status in the system to ‘inactive’ before handing the medicine to the patient.

“However, if the message comes back negative, there should be a reason for this, such as [the pack] has been recalled, withdrawn or dispensed elsewhere, and the pharmacist will have to take appropriate action.

Advantages  of FMD :

Once the NMVS is in place  or at least once some technical specifications are made available  pharmacy software system suppliers will need to build their interfaces to the national system. Pharmacies will need to invest in scanners and start to understand how workflows will change. New standard operating procedures will need to be written. There will be training requirements, as well as a need to understand how compliance with the FMD will be regulated.

Disadvantages of FMD :

This is a system originating from Europe that may not take account of UK anomalies. In Europe, for example, medicine packs are generally not split. But in the UK, packs are often opened and strips of tablets are shared between patients. Such practice does not sit easily with a system where a pack must be scanned and dispensed to a patient  if a box has been scanned once and the code decommissioned, a second scan for a second patient will trigger an alert.

For similar reasons, it is not clear how the FMD will work when community pharmacists prepare a seven-day supply of multiple medications for patients with co-morbidities.

Conclusion :

Timetable is not as tight as it looks. The FMD applies only to medicines manufactured after the 9 February 2019 implementation date and these won’t be in hospital or community pharmacy for quite some time & it will take years to get the system up and running.

There is a long way to go before anyone has a clear idea of what FMD in practice will look and feel like. There’s a mountain of work to do and a deadline by which to do it. The only certainty is this pharmacy processes are about to change  again.

Generics Drugs VS Branded Drugs and its Use in India you must Know

Generics Vs Branded Drugs

What are Generic Drugs:

Generic drugs are copies of brand-name drugs that have exactly the same dosage, intended use, effects, side effects, route of administration, risks, safety, and strength as the original drug. In other words, their pharmacological effects are exactly the same as those of their brand-name counterparts and  it  works in the same way and provides the same clinical benefit as its brand-name version.

What are Branded Drugs:

Branded drugs are the drugs that have a trade name and is protected by a patent (can be produced and sold only by the company holding the patent) and when the patent protection for a brand-name drug expires generic versions of the drug can be offered for sale if the FDA agrees.

Branded medicines are medicines which have a name given to them by a company for the purpose of advertising. Branded medicines may be the original medicine developed by a company or several companies may make the same generic medicine, to which each company gives its own brand name.

Why Generic Drugs are cheaper:

Generic makers don’t face the same costs as manufacturers of brand-name drugs. That is because the brand-name maker often invented the drug, a process that can cost hundreds of millions of dollars. That is an enormous economic advantage for these companies, which is why their drugs can be much cheaper.

Are Generic Drugs are Safe & same as Branded Drugs:

Yes. The FDA (Foods & Drugs Administration) requires that all drugs be safe and effective. Since generics use the same active ingredients and are shown to work the same way in the body, they have the same risks and benefits as their brand-name counterparts.

FDA requires drug companies to demonstrate that the generic medicine can be effectively substituted and provide the same clinical benefit as the brand-name medicine that it copies. The active ingredient in the generic medicine is the same as in the brand-name drug/innovator drug.

Why Branded Drugs are so expensive than Generic drugs:

According to the FDA, generic medications can cost, on average, 80 to 85 percent less than the brand-name equivalents. Brand-name drugs are typically more expensive because of the higher initial costs to develop, market, and sell a brand-new drug. A pharmaceutical company that develops a brand-name drug will file for a patent that prohibits other manufacturers from producing and selling the medication for a set time period.

Example of Generic & Branded Drugs:

An example of a generic drug, one used for diabetes, is metformin. A brand name for metformin is Glucophage. (Brand names are usually capitalized while generic names are not.) A generic drug, one used for hypertension, is metoprolol, whereas a brand name for the same drug is Lopressor.

Generic drugs must meet high standards to receive FDA approval:

FDA requires drug companies to demonstrate that the generic medicine can be effectively substituted and provide the same clinical benefit as the brand-name medicine that it copies. The abbreviated new drug application (ANDA) submitted by drug companies must show the generic medicine is the same as the brand-name version in the following ways:

  • The active ingredient in the generic medicine is the same as in the brand-name drug/innovator drug.
  • The generic medicine has the same strength, use indications, form (such as a tablet or an injectable), and route of administration (such as oral or topical).
  • The inactive ingredients of the generic medicine are acceptable.
  • The generic medicine is manufactured under the same strict standards as the brand-name medicine.
  • The container in which the medicine will be shipped and sold is appropriate, and the label is the same as the brand-name medicine’s label.

Do Generic drugs need Clinical Trial:

Today, more than 8 in 10 prescriptions filled in the United States are for generic drugs. … Because generic drug makers are not required to repeat the clinical trials of new drugs and generally do not pay for advertising, marketing and promotion, generics are usually substantially less expensive than brand-name drugs.

Use of Generic medicines in India:

Generic medicines in India have received a new impetus with Prime Minister Modi himself advocating the usage of these medicines. Doctors will now be required to prescribe generic formulations of medicines, as opposed to specific brands. The Prime Minister has announced that prescription of medicines by their generic names will be mandatory.

With increasing pressure from the “Big Pharma” companies in developed countries, Indian generic manufacturers must now operate under a markedly restrictive intellectual property rights (IPR) regime. The new policy can ensure that—at least in the Indian market—generic manufacturers retain an advantage. Big Pharma’s access to Indian consumers will have to be routed through generic companies using channels such as voluntary licensing.

Generic medicine Experiments in India:

The Tamil Nadu and Rajasthan governments procure generic name medicines at extremely competitive prices year after year, and crores of drugs are in use in their public health systems, thanks to the quality assurance systems in place.The success of the drug procurement system in these two states should counter the defeatist narrative that insists that generic medicines can never be good.This is not to underestimate the challenges in ensuring quality generic medicines countrywide, but the critics from the medical profession are doing the poor patient enormous disservice by swallowing the disinformation from the pharmaceutical industry about the general lack of bioavailability of generics as compared to brands.

When a pharma company invest & develop any new drug & earn patent rights for it, then is called branded drug(BD). The duplicates of branded drugs are known as generic drugs. They have following differences:

Production: Only Company with patent rights are allowed to manufacture Branded Drug. Once patent lapses, other companies are allowed to produce generic drugs.

Cost: Unlike generic drugs, branded drugs incur high cost due to high investment research & development.

Ingredients: The active ingredient (the one which cure the disease) of both drugs are same but the differs in colour, shape or taste

Affordable, effective & easy drug access important for “universal healthcare”. So, India has decided to bring a law for doctors to prescribe generic medicines which have certain issues:

  1. Implementation: Lower awareness and corruption have given rise nexus between Doctors chemists & pharma sector. So, public awareness via digital media along surveillance mechanism to curb nexus
  2. International pressure: Big western pharmaceutical lobbies may back stringent IPR rigme & compulsory licensing. They may blame India to breach TRIPS agreement and drag into WTO. But recent UN report has given precedence to human rights over patent rights which support India’s move for affordable generic price to improve health care
  3. Supply side challenge: India is import driven country for active pharmaceutical ingredient and already facing challenge of substandard quality of generic drugs. Along with this current move may reduce FDI inflow in pharm sector and slowdown research & development in domestic pharma companies. However, India has taken steps like ‘India Pharma & India Medical Device 2017’ and new IPR policy that offer incentive & ease of doing business in India. India should adopt stricter accreditation and inspection rules for generic drugs

Jan Aushadhi Scheme :

  • The Government has launched ‘Jan Aushadhi Scheme’ to make available quality generic medicines at affordable prices to all, especially the poor, throughout the country, through outlets known as Jan Aushadhi Stores (JASs).
  • Under the Jan Aushadhi Scheme, the State Governments are required to provide space in Government Hospital premises or any other suitable locations for the running of the Jan Aushadhi Stores (JAS).
  • Bureau of Pharma PSUs of India (BPPI) is to provide one-time assistance of Rs.2.50 lakhs as furnishing and establishment costs, start up cost for setting up a Jan Aushadhi Outlet.
  • Any NGO/Charitable Society/Institution/Self Help Group with experience of minimum 3 years of successful operation in welfare activities, can also open the Jan Aushadhi store outside the hospital premises. A margin of 16% on the sale price is built in the MRP of each drug.
  • In addition, the JAS are eligible for incentive linked to sale of medicines @ 10% of monthly sales amount, subject to a ceiling of Rs.10,000/- pm for a period of first 12 months. In case of Stores opened in North Eastern States and other difficult areas i.e., Naxal affected areas/Tribal areas etc., the rate of incentive is15% of monthly sale amount, subject to a ceiling of Rs.15,000/- per month.
  • At present more than 175 Jan Aushadhi Stores have been opened across various States/UTs. JAS are opened on the locations as requested by the entity intending to open. The steps are also taken to open Jan Aushadhi stores in all AIIMS, prominent Hospitals, Medical Colleges under the Ministry of Health & Family Welfare.

       Indian Government Initiative:

  • The Medical Council of India (MCI), in an amendment to the Code of Conduct for doctors in October 2016, has recommended that every physician “should prescribe drugs with generic names legibly … and he/she shall ensure that there is a rational prescription and use of drugs.”
  • How the MCI is going to ensure rational prescription and use, without a framework to measure the same, should be looked into seriously.
  • Rational use and prescription depends on the doctor, the pharmacist, the regulator, and the consumer.
  • Some minimum prerequisites for rational use are: prescription-only medicines (Schedules G, H, H1 and X) must not be available freely over the counter; doctors and their professional bodies along with regulators must ensure there is no misuse of antibiotics and critical drugs; and the removal of all irrational/harmful/useless medicines, both FDCs and unscientific single ingredients, must be ensured.
  • Practical guidelines for rational use and prescription audit of medicines must be developed and implemented seriously by all doctors. Branding of off-patent drugs needs to be discouraged as is the practice in well-regulated countries.
  • A time bound plan to make generic prescriptions mandatory will also prepare Indian pharma’s vast supply chain of 800,000 wholesalers and retailers to get used to the new initiative progressively. India’s 800,000 retailers have thrived because it is a profitable high-margin business.

Conclusion :

  1. In the comparative analysis of generic drugs over the Branded drugs, the analysis were  made based on how they were developed. Branded drugs take lots of time to get approved as the new substance drug undergoes lots of testings (pre clinical as well as clinical testings). Also, the analysis was made based on the costs. Branded drugs are more expensive as seen in the cost estimate above. Generic drugs are cheaper option especially for long term treatments.
  2. People are not aware of word “generic medicine” because they do not know what the word “generic” means. Many think its some different system of medicine – just like ayurveda, homeopathy, allopathy, unani, etc – they think a new system of medicine has been discovered and approved. So awareness among the people about generic drugs is more important & should be increased in order to get the medicines in cheaper rates.
  3. Ministry of Health & Family Welfare of India & Health department of the respective states should watch that whether Jan Aushadhi sceheme is implemented in all the states & people are getting its benefit or not.
  4. Every physician should prescribe drugs with generic names legibly and he/she shall ensure that there is a rational prescription and use of drugs.

Indian Pharma Company Vision and Challenges

Introduction:

The Indian pharma industry has been growing at a compounded annual growth rate (CAGR) of more than 15% over the last five years and has significant growth opportunities. However, for the industry to sustain this robust growth rate till 2020, companies will have to rethink their business strategy.

India’s pharmaceutical industry has grown by Rapidly or in fast progress in the last three decades. As a result, it has emerged as world’s 3rd largest producer of drugs in terms of volume & 6th largest pharmaceutical market globally by its size. The industry has posted double-digit growth over the last few years, rising to US $36.7 Billion (Rs 3670 crores) in 2017 and projected to grow to US $55 Billion (Rs 5500 crores) by 2020, from US $20 billion (Rs 2000 crores) in 2015.

India is the largest provider of generic drugs globally. Indian pharmaceutical sector industry supplies over 50 per cent of global demand for various vaccines, 40 per cent of generic demand in the US and 25 per cent of all medicine in UK.

Indian companies received 304 Abbreviated New Drug Application (ANDA) approvals from the US Food and Drug Administration (USFDA) in 2017 as compared to 201 ANDA approvals in 2016. The country accounts for around 30 per cent (by volume) and about 10 per cent (value) in the US$ 70-80 billion US generics market.

India’s biotechnology industry comprising bio-pharmaceuticals, bio-services, bio-agriculture, bio-industry and bioinformatics is expected grow at an average growth rate of around 30 per cent a year and reach US$ 100 billion by 2025.

Investments and Recent Developments:

The Union Cabinet has given its nod for the amendment of the existing Foreign Direct Investment (FDI) policy in the pharmaceutical sector in order to allow FDI up to 100 per cent under the automatic route for manufacturing of medical devices subject to certain conditions.

The drugs and pharmaceuticals sector attracted cumulative FDI inflows worth US$ 15.83 billion between April 2000 and June 2018, according to data released by the Department of Industrial Policy and Promotion (DIPP).

Some of the recent developments/investments in the Indian pharmaceutical sector are as follows:

  • In August 2018, the market grew by 8.7 per cent year-on-year with sales of R s 11,342 crore (US$ 1.69 billion).
  • During April-June 2018, pharmaceutical sector in India witnessed private equity and venture capital investments of US$ 396 million.
  • In 2017, Indian pharmaceutical sector witnessed 46 merger & acquisition (M&A) deals worth US$ 1.47 billion.
  • The exports of Indian pharmaceutical industry to the US will get a boost, as branded drugs worth US$ 55 billion will become off-patent during 2017-2019.

Indian Government take responsibility in Pharma :

Some of the initiatives taken by the government to promote the pharmaceutical sector in India are as follows:

  • The National Health Protection Scheme is largest government funded healthcare programme in the world, which is expected to benefit 100 million poor families in the country by providing a cover of up to Rs 5 lakh (US$ 7,723.2) per family per year for secondary and tertiary care hospitalization. The programme was announced in Union Budget 2018-19.
  • In March 2018, the Drug Controller General of India (DCGI) announced its plans to start a single-window facility to provide consents, approvals and other information. The move is aimed at giving a push to the Make in India initiative.
  • The Government of India is planning to set up an electronic platform to regulate online pharmacies under a new policy, in order to stop any misuse due to easy availability.
  • The Government of India unveiled ‘Pharma Vision 2020’ aimed at making India a global leader in end-to-end drug manufacture. Approval time for new facilities has been reduced to boost investments.
  • The government introduced mechanisms such as the Drug Price Control Order and the National Pharmaceutical Pricing Authority to deal with the issue of affordability and availability of medicines.

Challenges for Indian Pharma Industry :

  • Keeping in mind the sheer number of SRA (Stringent Regulatory Authority) approved facilities in India the pharma industry is bound to become the centre of attention by many regulatory authorities. Currently, there is a fierce increase in the number of companies receiving a notice or warning letters or Import alert by USFDA & MHRA .
    • The Local Regulatory body i.e. Central Drugs Standard Organization (CDSCO) and State Foods & Drugs Administration (FDA) needs to get Accredited by WHO and India should join PICs, this will automatically raise the bar of local regulators. We cannot expect our companies and facilities to be world class while our regulators are way behind.
    •  Proactive quality approach – while many pharma companies in India are already working in this direction, the challenge is to get the industry thinking on these lines, as well. International requirements of ADR, Pharmacovigilance etc. should be made mandatory for domestic markets, too. At present, 70 to 80 per cent pharma companies maintain this infrastructure for international markets. Making it mandatory for domestic market as well will increase the quality perception of Indian market in International arena.
    • Today, one of the biggest concerns of International clients, regulators and agencies is quality of Indian medicines. Internationally, India’s generic medicine industry has been questioned for compromising on product quality.
    • Until product quality control is not introduced in the domestic market, India’s international image will not improve. The country’s medicine industry has to put its house in order and the government should monitor it stringently.
  • with the Indian pharma industry’s personnel turnover at 33 per cent, every three years, there is a completely new staff in a company. The attrition rate in the pharma industry is extremely high. Pharma is one of the world’s most paperwork-intensive industries. It is also one of the world’s most scrutinised industries. So how does a company maintain quality in the absence of skilled staff? In my experience of having worked in the industry for 12 years, I have noticed a general lack of responsibility amongst people. They don’t want to take responsibility for their actions.
    • To train a single person on good manufacturing practices for pharmaceutical products – GMP principles takes one year and training costs. This trained person can only start contributing positively by the 2nd year and by this point he is already looking for another job in the market. If we intent to pay attention to quality, this is impossible until the brain drain in the industry is not addressed.
    • As we know, the key purpose of the Drug Price Control in India is to ensure adequate access to essential medicines for the common man. To achieve this objective meaningfully, the process that the price regulator should follow must always ensure that all such medicines are: Adequately available and reasonable affordable sot therefore, maintaining a right balance between ‘affordability’ and ‘availability’ of  medicines, while framing any drug policy, is of critical importance.

Conclusion :

  • Today, in the given situation, the future of the industry depends on how we react and address today’s challenges. In order to strengthen the ties of the pharma industry, we need a national policy on pharmaceuticals and government’s intervention is the areas needed.
  • If remedial measures are not taken, sooner than later, to overcome these major challenges  both by the pharmaceutical industry and the government working in tandem, it will be difficult for the industry to take a large increase in the foreseeable future, as is being envisaged by many.

ICH Guideline Q1 to Q14

What is ICH Guidelines :
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is a project that brings together the regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects.
What are the purpose of ICH Guidelines :
The purpose of ICH is to reduce or eliminate the need to duplicate the testing carried out during the research and development of new medicines by recommending ways to achieve greater harmonization in the interpretation and application of technical guidelines and requirements for
product registration.

  • ICH Q1 to Q14
Q1A Stability testing of  new drug substances and products
Q1B Stability testing: photo stability testing of new drug substances and products
Q1C Stability testing for new dosage forms
Q1D Bracketing and matrixing designs for stability testing of new drug substances and products
Q1E Evaluation for stability data
Q2 Validation of analytical procedures: text and methodology
Q3A Impurities in new drug substances
Q3B Impurities in new drug products
Q3C Impurities: guideline for residual solvents
Q4 Pharmacopoeias
Q5B Quality of biotechnological products: analysis of the expression construct in cells used for production of r-dna derived protein products
Q5C Quality of biotechnological products: stability testing of  biotechnological/biological    products
Q5D Derivation and characterization of cell substrates used for production of biotechnological/biological products
Q5E Comparability of biotechnological/biological products subject to changes in their Manufacturing process
Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances
Q6B Specifications: test procedures and acceptance criteria for  biotechnological/biological products
Q7 Good Manufacturing practice for API (GMP)
Q8 Pharmaceutical development
Q9 Quality Risk Management (QRM)
Q10 Pharmaceutical Quality System (PQS)
Q11 Development & Manufacture of Drug substance (DMDS)
Q12
Technical & Regulatory Considerations for Pharmaceutical Product Lifecycle Management
Q13 Continuous Manufacturing for Drug Substances and Drug Products
Q14 Analytical Procedure Development and Revision of Q2 (R1)
Analytical Validation
ICH Q1 to Q14

Pharma Abbreviations

PVP : Process Validation Protocol
PVR : Process Validation Report
CVP : Cleaning Validation Protocol
CVR : Cleaning Validation Report
MQRM : Monthly Quality Review Meeting
QRM : Quality Risk Management
UCL : Upper control Limit
LCL : Lower control Limit
IPQA : In process Quality Assurance
LLC : Live line clearance
API: Active pharmaceutical ingredient
APQR: Annual product Quality review
AQL: Acceptable quality level
ASM: Active Substance Manufacturer
ASMF: Active Substance Master File
AST: Accelerated stability testing
CRT : Controlled Room Temperature
ASTM: American Society for Testing and Materials
BA: Bioavailability
BE : Bioequivalence
BET: Bacterial Endotoxin Test
BMR: Batch Manufacturing Record
BOD: Biological Oxygen Demand
BOM: Bill of Materials
BOPP: Biaxially Oriented Polypropylene
BP: British Pharmacopoeia
BPR:  Batch Packaging Record
BSE: Bovine spongiform encephalopathy (mad cow disease)
CAPA: Corrective and preventive action
FMEA : Failure mode & Effect Analysis
RCA : Root cause Analysis
CBE: Changes being effected
CBER: Center for Biologics Evaluation and Research (FDA)
CCIT: Container closure integrity test
CDER: Center for Drug Evaluation and Research (FDA)
CDSCO: Central drug standard control organization (India)
CEP:Certification of suitability of European Pharmacopoeia monograph
GC   : Gas Chromatography
HSA: Health Sciences Authority, Singapore
ANVISA: Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency Brazil
TGA: Therapeutics goods administration (Australia)
USFDA: United states foods and drugs administration 
FDA: Food and Drug Administration, United States
WHO: World Health Organisation
JP: Japanese Pharmacopoeia
MHRA: Medicines and Healthcare products Regulatory Agency (UK)
MEDSAFE: Medicines & medicinal devices safety authority (New zealand)
CQA: Critical Quality Attribute
MACO : Maximum allowable Carry over
ADE: Adverse drug event
PDE : Permitted Daily Dosage Exposure
ACU: Air Cooling  Unit
AHU: Air Handling Unit
ANDA: Abbreviated new drug application
NDA : New drug application
EDMF: European drug master file
EDQM: European Directorate for the Quality of Medicines
EH&S: Environmental health and safety
EIR: Establishment inspection report (FDA)
EMEA: European Medicines Agency
EP: European Pharmacopoeia
ETP: Effluent Treatment Plant
EU: Endotoxin unit
EU: European Union
URS: User Requirement Specification
FAT: Factory Acceptance Testing
SAT : Site Acceptance Test
IQ : Installation Qualification
DQ : Design Qualification
OQ : Operational Qualification
PQ: Performance Qualification
FBD: Fluid-bed dryer
FBP: Fluid-bed Processor
RMG : Rapid mixer Granulator
FDC: Fixed Dose Combination
FEFO: First expiry first out
FG: Finished Goods
FIFO: First in first out
FMEA: Failure modes and effect analysis
FOI: Freedom of information
GAMP: Good automated manufacturing practice
GC: Gas Chromatography
GCLP: Good clinical laboratory practice
GCP: Good clinical practice
GDP: Good distribution practice
GEP: Good engineering practice
DOP: Dioctyl Phthalate
GIT: Gastrointestinal Tract
GLP: Good laboratory practice
GMO: Genetically modified organism
GMP: Good manufacturing practice
GPT: Growth Promotion Test
GRAS/E: Generally recognized as safe and effective
GRP: Good review practice
HACCP: Hazard analysis critical control point
HDPE: High Density Polyethylene
HEPA: High efficiency particulate air (filter)
HPLC: High performance liquid chromatography 
DHS : Dry heat sterilization
HVAC: Heating, ventilating, and air conditioning
ICH: International Conference on Harmonisation
IH: In house
IM: Intramuscular
IND: Investigational new drug
INDA: Investigational new drug application
IP: Indian Pharmacopeia
IPA: Isopropyl Alcohol
IPS: In process control
IQ: Installation qualification
IR: Immediate release
ISO: International Organization for Standardization
ISPE: International Society for Pharmaceutical Engineering
IV: Intravenous
KOS: Knowledge organization system
LAF: Laminar air flow
LAL:  Limulus Amoebocyte  Lysate
LD: Lethal dose
LD50: Lethal dose where 50% of the animal population die
LDPE: Low Density Polyethylene
LIMS: Laboratory Information Management System
LIR:  Laboratory Investigation Report
LOD: Loss on drying
LOD: Limit of detection
LOQ: Limit of quantification
LR: Laboratory Reagent
LVPs: Large Volume Parenterals
MA: Marketing Authorisation
MAA: Marketing Authorisation Application
MAC: Maximum Allowable Carryover
MCC: Medicines control council (South Africa)
MDD: Maximum daily dose
MFR: Master Formula Record
WL: Warning letter
MOA: Method Of Analysis
MSDS: Material Safety Data Sheets
NCE: New chemical entity
NDA: New Drug Application
NF: National Formulary
NIR: Near Infra Red Spectroscopy
NON: Notice of non-compliance (Canada)
ODI: Orally Disintegrating Tablet
OQ: Operation Qualification
OSD: Oral Solid Dosage
OSHA: Occupational Safety And Health Administration
OTC: Over-the-counter
OOS: Out of specification
OOT: Out of trend
PAC: Post-approval changes
PAO: Poly alpha olefin
PAT: Process Analytical technology
PET: Preservative efficacy test
PLC:  Programmable Logical Control
PVC: Polyvinyl Chloride
PVDC: Polyvinylidene Chloride
PW: Purified Water
QBD : Quality by design
QM: Quality Manual
QMS: Quality Management System
RH: Relative humidity
RLAF: Reverse laminar air flow
RLD: Reference listed drug
RM: Raw material
RM: Packing material
FGS: Finished Goods Store         
BSR: Bounded store Room
RO: Reverse Osmosis
RS: Related Substance
SAT: Site Acceptance Testing
SIP: Sterilization in place
SIP:  Steam in place
SLS: Sodium Lauryl Sulphate
SMF: Site master file
SOP: Standard operating procedure
SPE:  Society for Pharmaceutical Engineering
SUPAC: Scale-up and post approval changes
SVP:  Small Volume Parenteral
TDS: Total Dissolved Solids
TOC: Total organic carbon
TSE: Transmissible spongiform encephalopathy
USP: United States Pharmacopeia
USP-NF: United States Pharmacopeia-National Formulary
CMS: Continuous monitoring system
VMP: Validation Master Plan
WFI: Water for injection
TRF : Test Request Form
CFR: Code of Federal Regulations
CFU: Colony Forming Unit
cGMP: Current Good Manufacturing Practices
CIP: Clean in place
COA: Certificate of analysis
MOA: Method of analysis
COS: Certificate of suitability
COPP: Certificate of Pharmaceutical Products
CPP: Critical Process Parameter
DMF: Drug master file