As you know in pharmaceutical industry there are various departments like Production, Quality Control, Quality Assurance, Engineering, Technology Transfer, Warehouse, Research and development and Human resource Department etc.

Refer Production Personnel Responsibilities : https://pharmaceuticalupdates.com/2020/06/23/responsibilities-of-production-personnel-in-pharmaceuticals/

Refer Quality Assurance Personnel Responsibilities : https://pharmaceuticalupdates.com/2019/01/26/responsibility-of-quality-assurance-personnel-or-quality-unit-in-pharmaceuticals/

Refer Quality Control Personnel Responsibilities : https://pharmaceuticalupdates.com/2020/05/02/responsibilities-of-quality-control-personnel/

Warehouse or Stores are the department in pharmaceuticals where Raw material (Active & Excipients) and Packing materials which are used in the manufacturing of batches shall be received and stored at required storage condition.

After final packing products are stored in Finished Goods stores of warehouse and after Quality control and Quality Assurance released products are dispatched to market.

Following are the job responsibilities of Warehouse personnel and this topic will help to the freshers as well as Experience personnel to gain some basic knowledge in Pharmaceuticals.

1. To maintained Warehouse and Finished Goods area clean and presentable for audit.

2. To follow Good Documentation practices and safety instructions & ensure compliance while working in warehouse.

3. Receiving of Raw materials and Packing materials and Prepare Goods receipt Note (GRN)

4. Recording of Temperature, Relative Humidity and Differential Pressure in stores and Finished Goods area.

5. Arrangements of Raw material and Packing material in stores according to the status i.e Under test Approved, Rejected and Quarantine etc.

6. Dispensing and issue of Raw materials and Packing materials to production and Packing department as per respective Batch manufacturing and Packing record.

7. Filling the Equipment Logbooks and area logbooks and entries in Batch manufacturing and Packing record after dispensing. 

8. To perform the Calibration and Verification of Weighing balances.

9. Ensure compliance with current Good manufacturing Practice (cGMP) in warehouse.

10. Manpower handling in warehouse department.

11. Physical verification of stocks as per Standard Operating procedure.

12. Follow up with Quality control department for timely sampling and release of materials.

13. Preparation of Standard Operating Procedure related to warehouse department.

14. To provide SOP Training to juniors or new joining persons.

15. Responsible for Handling of Change control and Deviations.

16. Prepare packing list and dispatch plan for Finished Goods and dispatch of Finished Goods.

17. Identify the materials which are due for Retesting on monthly basis and inform to respective department for sampling of the same.

18. Handling of Damaged, Rejected and Expired materials in warehouse.

19. To follow online documentation in Raw material, Packing material and Finished Goods store.

20. Follow up with purchase and commercial department for disposal of non moving, obsolete and rejected raw and packing materials.

21. Temperature mapping in Stores and Finished Goods area.

22. Posting and Transaction of materials in SAP or ERP system.

Each departments have their own responsibilities in Pharmaceutical and based up on the job responsibility every body has to work.

Job responsibility shall be assigned to the persons based upon Educational Qualification and Experience and according to the job responsibility every body has to take Standard Operating Procedure (SOP) Training.

Following are the job responsibilities of Production personnel and this topic will help to the freshers as well as Experience personnel to gain some basic knowledge in Pharmaceuticals.

1. To maintained Manufacturing and packing area clean and presentable for audit.

2. Recording of Temperature, Relative Humidity and Differential Pressure in Manufacturing and Packing area.

3. Filling the Equipment and Instrument Logbook in Manufacturing and Packing area. 

4. Ensure compliance with current Good manufacturing Practice (cGMP) on shop floor.

5. To follow Good Documentation practices and safety instructions & ensure compliance while working in manufacturing and Packing area.

6. Operating the machines as per product requirements and Manpower handling in Production and Packaging department.

7. Filling of Batch Manufacturing and Batch Packing Record in Manufacturing and packing area.

8. To perform Daily or Monthly weighing Balance calibration or verification in Manufacturing and Packing area.

9. To procure, receive and manage all change parts, Stereos, Sieves, Screens, Finger bags, Punches, Dies etc for Manufacturing and Packing area.

10. Planning and execution of batches to be manufactured in process and Packaging area.

11. To maintain and Fill the documents online and review the documents like Manufacturing and Packing Records.

12. Review of Batch Manufacturing Record (BMR), Batch Packing Record (BPR), Master Formula Record and Master Packing Record.

13. Execution of process equipment qualification by coordinating with qualification team and vendor.

14. Preparation or Review of Failure investigation, Market complaint investigation, Change control, Deviation, Out of Specification and investigation routed through Quality Management System (QMS).

15. To initiate Change Control if required and Fill Deviation form in case of any Non conformance

16. Review protocols and reports for cleaning, Process validation, Mapping, Hold time study and qualifications etc.

17. To ensure for completion of Preventive maintenance as per schedule. 

18. Responsible for compliance for all types of regulatory audits , Inspection and/ or internal quality audit

19. Preparation of Job responsibility for Production and Packaging personnel.

20. Preparation of Standard Operating Procedure in Manufacturing and Packing Area.

21. To Provide SOP Training to the sub-ordinates and newly joined personnel.

22. Section wise allocation of work to sub-ordinates.

23. Ensure implementation of Pest control program at site.

24. Control of Plant Hygiene and manufacturing environment and environmental monitoring in area .

25. To ensure the completion of Monthly Training for Production and Packaging personnel.

26. SAP and ERP Transaction related to Manufacturing and Packaging department.

27. To implementation of Corrective and Preventive Action at shop floor.

28. To guide or Explain the Auditors and External persons about the manufacturing and Packing area if required.

29. To coordinate with other departments like Engineering, Quality assurance, Warehouse and Quality Control for smooth running of manufacturing and Packing activities.

Copy the above contents may be subject to copy writing and not allowed

Refer responsibilities of Quality Assurance : https://pharmaceuticalupdates.com/2019/01/26/responsibility-of-quality-assurance-personnel-or-quality-unit-in-pharmaceuticals/

Below are the general procedure for good controls and practices for Packaging Activities in Pharmaceuticals and the persons working in packing department should follow the procedure for better control and compliance.

Every person should follow personnel entry and exit procedure for entry and exit in Packing Area as per SOP (Standard Operating Procedure).

For SOP Pl refer : https://pharmaceuticalupdates.com/2019/02/02/standard-operating-procedure-sop-of-standard-operating-procedure-sop/

Before starting any operation, personal hygiene, product safety and area cleanliness must be checked by the concerned packing personnel.

Entries in BPR (Batch Packing Record) should be done timely and neatly and BPR should be checked for its Batch No., Batch size, Product code, Market, Shelf Life, pack size and Storage condition etc.

Ensure Cleaning and line clearance of machines and area as per respective SOP’s and ensure that the machine setting is done as per respective SOP’s.

Check the release status of bulk/semi-finished product with batch no. Weigh and verify gross weight of each container against the product label on it.

Check the Product name and batch no. on each container and bring it to respective packaging line planned for packing after line clearance.

Always load the containers of the bulk product in the product hopper in serial order/Lot wise and Attach labels of bulk containers in BPR.

Check for product name, strength, count and batch no. on dispensed packaging Material before bringing the material on to the packing line.

Always keep the packing materials of one batch in a cage trolley or in a pallet with required label to avoid mix up with other product or batch.

Remove and verify the dispensed packaging material labels for material code, A.R.No., Dispensed quantity, Batch No., Count against Packaging Material Requisition and Dispensing Record and attach the labels in BPR after verification.

All rejects observed on packing line should be kept in crates / reject bins / poly bags with appropriate status labels and at the end of batch destroy rejects as per SOP .

Persons on packing line should be vigilant and shall perform their activities with full concentration and ensure that there is streamline flow of packs on packing line with appropriate packing controls.

If required provide break to the persons working in packing line .

Packing material rejects found (if any) on the packs should be informed to the line executive/technician and ensure that all the rejected packs are put in the crates.

Ensure that individual carton is checked for proper overprinting quality on it and ensure that a set of cartons per insertion into the shipper (can vary as per the shipper fill value).

Ensure that individual filled shipper is weighed for its fill value and is stacked on the pallet and ensure that if the balance detects short or excess carton on display it should be informed to the line executive and ensure that shipper number and weight is properly written on the shipper.

Initial checks and operating specifications shall be check and record in BPR as per instructions mentioned in BPR.

Reconcile all packaging material after sample quantity written by QA in BPR at the end of batch.

If any excess packaging material is required for the batch, shall be issued from warehouse and Balance packaging materials (if any) are returned to ware house through Packing Material Return Note.

If there is any partially filled shipper in the department at the time of closing, it shall  be sealed partially with BOPP tape and It shall be kept on table and It shall be checked by Officer next day morning before starting the line.

End of batch / Partial packing of batch shall be transfer to finished goods warehouse through Packed Goods Transfer Note.

For any breakdown of equipment or maintenance give the intimation to the Engineering Department.

If any cancellation is to be done in any packing document, It should be strike off by a single line and it must be signed with date by concerned person and Overwriting is not permitted in any document.

Any incident or deviation shall be immediately reported to QA by logging it and the same shall be investigated through incident report.

Usage and cleaning logs should be maintained for all the equipment.

Guideline for closing of Blister packing lines during breaks (Tea/Lunch/Dinner):

Ensure that product is not present on the sealing station of machine and the packs are removed from the machine conveyor.

Ensure that hopper and bowl are covered properly and Put off the machine.

Ensure that product fallen down (if any) on the floor are removed and put in rejection bin and ensure that the poly bags containing products are tied or fastened properly.

Put off the conveyor belt and Check the good packs/rejected packs are kept properly in the respective containers and ensure that filled cartons are overprinted.

Ensure that there are no partially filled cartons on the conveyor/table and  Put off the lights of the area and Finished goods are transfer to Warehouse as per packed goods transfer note.

Training plays an important role in any industry and it gives a clear understanding about the roles and responsibilities of a person working in an organization.

There are different types of Training which are as follows

(1)  Induction Training

(2)  On Job Training

(3)  Self Reading Training

(4)  Class Room Training

(5)  External Training

(6)  Incidental Training

(7)  Refresher Training

Induction Training:

Training given to the new joinee (Employee) at the time of joining the organization for awareness of organization and organization personnel is termed as Induction Training.

Whenever a new employee is joining the organization, on completion of joining procedure, Personnel – HRA shall give him / her first-hand information regarding the company’s profile, group activities, service benefits, service rules, administrative rules, disciplinary rules and personnel hygiene.

 Human Resource department shall also provide “Induction Manual” for awareness of organization.

On completion of reading of “Induction Manual”, Personnel – HRA shall take him / her for plant round to familiar with plant as well as plant personnel.

On Job Training :

Training given to an employee at the work place is termed as On Job Training.

On completion of Induction Training and Departmental Training, department head or section head or his / her designee shall give “On Job Training” to new employee at work place to understand the practical procedure regarding his / her work profile.

In case an employee does not qualify in his / her performance, training need is assessed by the superior and “On Job Training” shall be given to employee again.

Self Reading Training :

The effects of reading strategy instruction, called Self Reading Training and also self reading training includes explaining the meaning of information to self while reading.

Only qualified trainers shall be read SOPs and cGMP modules and understand the information / instruction given in that.

Class Room Training :

Training given to an employee in class room or other than work place is termed as Class Room Training.

For the training program, employees will gather at the designated location

Faculty shall give training in English and / or Hindi language to all employees and along with training, wherever required training material shall be given to all employees.

External Training : 

Training given to employee outside the plant location / by the person other than the Organization Group is termed as External Training.

Human Resource & Administration department with consultation of all department heads shall prepare employee list for external training program

Incidental Training : 

Training given to employee with respect to incident to aware the severity / harm of particular incident.

In case some incident happens in the plant, such type of the training shall be conducted for the concerned personnel and Incidental Training Program shall be announced on emergency basis.

Refresher Training : 

Training given to an employee at a defined frequency to freshen-up the knowledge is termed as Refresher Training.

The Purpose of refresher training is to ensure that skills among staff remain sharp and that previous learning are retained and kept current.

Apart from the training schedule/calendar, cGMP and other refresher SOP training shall be also conducted throughout the year periodically for the completion of training for remaining persons.

It is our responsibility to follow the below mentioned principles wherever possible and the government is also using these principles as the basis of discussions with businesses, unions, local government and many other stakeholders, to agree how the principles should apply in different settings to make them safer.

All of us, as customers, visitors, employees or employers need to make changes to lower the risk of transmission of the corona virus.

1. Keep your distance from people outside your household

Although identify this will not always be possible, it is important to be aware that the risk of infection increases the closer you are to another person with the virus, and the amount of time you spend in close contact with them.

Public Health England recommends trying to keep two metres away from people as a precaution.

However, this is not a rule and the science is complex and the key thing is to not be too close to people for more than a short period of time, as much as you can.

2. Keep your hands and face as clean as possible

Wash your hands often using soap and water, and dry them thoroughly.

Where available, use sanitizer outside your home, especially as you enter a building and after you have had contact with surfaces.

Avoid touching your face.

3. Work from home if you can

With the proper equipment and adjustments, many people can do most or all of their work from home.

Your employer should support you to find reasonable adjustments to do this, However, not all jobs can be done from home.

If your workplace is open and you cannot work from home, you can travel to work.

4. Avoid being face-to-face with people if they are outside your house

You are at higher risk of being directly exposed to respiratory droplets (released by talking or coughing) when you are within two meters of someone and have face-to-face contact with them.

You can lower the risk of infection if you stay side-to-side rather than facing someone.

5. Reduce the number of people you spend time with in a work setting

You can lower the risks of transmission in the workplace by reducing the number of people you come into contact with regularly, where you can.

 Your employer can support with this (where practical) by:

• changing shift patterns
• splitting or dividing people into smaller, contained teams

6. Avoid crowds

You can lower the risks of transmission by reducing the number of people you come into close contact with i.e. avoid peak travel times on public transport, where possible.

Businesses should also take reasonable steps to avoid people being gathered together i.e. by allowing the use of more entrances and exits, and staggering entrance and exit, where possible.

In the shopping malls also don’t allow the people to gather at one place and shopping mall employees should take rounds continuously to avoid this.

7. If you have to travel (for example, to work or school), think about how and when you travel

To reduce demand on the public transport network, you should walk or cycle wherever possible. If you have to use public transport, you should try to avoid peak times.

Employers should consider staggering working hours, expanding bicycle storage facilities, providing changing facilities and providing car parking.

8. Wash your clothes regularly

There is some evidence that the virus can stay on fabrics for a few days, although usually it is shorter, therefore if you are working with people outside your household, wash your clothes regularly.

Changing clothes in workplaces should only be considered where there is a high risk of infection or there are highly vulnerable people, such as in a care home.

 If you need to change your clothes, avoid crowding into a changing room.

9. Keep indoor places well ventilated

Evidence suggests that the virus is less likely to be passed on in well-ventilated buildings and outdoors.

In good weather, try to leave windows and doors open in areas where people from different households come into contact, or move activity outdoors if you can.

Use external extractor fans to keep spaces well ventilated and make sure that ventilation systems are set to maximize the air flow rate.

Heating and cooling systems can be used at their normal temperature settings.

10. Face coverings

If you can, wear a face covering in enclosed public spaces where social distancing isn’t possible.

This is most relevant for short periods indoors in crowded areas, for example, on public transport or in some shops or vegetable market etc.

In countries like UK, USA and india  you must wear a face covering on public transport and you should be prepared to remove your face covering if asked to do so by police officers and staff for the purposes of identification.

Evidence suggests that wearing a face covering does not protect you. However, if you are infected but have not yet developed symptoms, it may provide some protection for others you come into close contact with.

Face coverings do not replace social distancing If you have symptoms of COVID-19 (cough, and/or high temperature, and/or loss of, or change in, your normal sense of smell or taste – anosmia), you and your household must isolate at home and you should arrange to have a test to see if you have COVID-19.

A face covering is not the same as the surgical masks or respirators used by healthcare and other workers as part of personal protective equipment.

These should continue to be reserved for those who need them to protect against risks in their workplace, such as health and care workers, and those in industrial settings, like those exposed to dust hazards.

Face coverings should not be used by children under the age of 3 or those who may find it difficult to manage them correctly.

It is important to use face coverings properly and wash your hands before putting them on and taking them off.

You can make face-coverings at home and it should cover the mouth and nose.

11. When at work, follow the advice given to you by your employer

Employers have a duty to assess and manage risks to safety in the workplace.

The government has issued guidance for employers and businesses on corona virus which includes guidance on how to make adjustments to your workplace to help you maintain social distancing.

It also includes guidance on hygiene, as evidence suggests that the virus can exist for up to 72 hours on surfaces. Therefore, frequent cleaning is particularly important for communal surfaces like:

• door handles
• lift buttons
• communal areas like bathrooms
• kitchens
• tea points

Reference: https://www.gov.uk/government/publications/staying-safe-outside-your-home/staying-safe-outside-your-home

These temporary good manufacturing practice (GMP) flexibilities will be allowed to address the current exceptional circumstances.

These flexibilities will enable manufacturers to release additional quality system capacity for to focus on ensuring continuity of supply using quality risk management principles

Manufacture and importation

Where appropriate based on risk, testing of raw materials may be limited to identification only where supplier history, material criticality, and the finished product quality control strategy permits. In these situations, reliance may be placed on the qualified supplier’s certificate of analysis for other quality attributes.

Based supplier history, material criticality, and the finished product quality control strategy permits, material shall be released based on supplier certificate of analysis & quality risk assessment.

For Raw materials and Packing materials where outside testing is applicable and not able to perform due to transportation restriction results of analysis of last consignments received shall be checked and material will be released based on in-house test results and release data of vendor.

Testing results for parameters applicable for outside testing shall be taken from Vendor COA and Vendor should be approved vendor.

The analysis of pending in-house tests shall be completed before QP release of the particular batch

Product may be shipped from a manufacturing site under quarantine whilst quality control tests and batch certification at manufacturer are ongoing with system in place to ensure that the product is not placed on the market until it has been QP certified.

In such case batch can be released under quarantine for dispatch as per the market requirement and Certificate of conformance (COC) will be issued after completion of all materials and Finished Product testing.

Pharmaceutical Quality System

Management of non-conformances and incidents after completion of a QA assessment to determine product impact, investigation of ‘minor’ events may be put on hold and these should be tracked, with investigations initiated in response to any identified trend.

Supplier audits may be put on hold and these should be re-prioritized based on risk when travel restrictions are lifted.

Routine SOP reviews may be extended

Internal audit (self-inspection) and GMP refresher training may be put on hold

Post inspection regulatory commitments relating to deficiencies classified as ‘Other’ may be put on hold and these should be recorded in the quality system and corrected post pandemic

Reporting use of these flexibilities

The Qualified Person should be involved in decisions to implement any GMP flexibilities.

Where flexibilities are used, they should be reportedto Covid19.GMDP@mhra.gov.uk.

Medicines being marketed outside the UK

If the medicine might also be marketed outside the UK, and/or if the manufacturer is operating under a manufacturing authorization granted by another medicines competent authority, the report must also be sent to the competent authority of the relevant market.

Reporting any difficulties to us

If manufacturers find that these measures are not providing enough flexibility to deal with the current logistical challenges quickly, please report this to Medicines and Healthcare Products Regulatory Agency (MHRA) UK as soon as possible.

Reporting any difficulties will help MHRA UK to monitor the national situation in real time, ensuring MHRA can take actions that support supply chains and address common difficulties as situations change.

MHRA rely upon any difficulties being reported and can take quick steps to adjust the regulatory system.

This will ensure MHRA can meet the needs of the system and fully support critical supply chains, whilst continuing to protect public health.

Report any difficulties to MHRA Customer Services Centre by calling 020 3080 6000 or email info@mhra.gov.uk.

Reference : https://www.gov.uk/guidance/exceptional-gmp-flexibilities-for-medicines-manufacturers-during-the-coronavirus-covid-19-outbreak

Due to the COVID-19 pandemic, remote working has increased and some organizations have advised that their processes for approving paper documents with wet ink signatures are no longer achievable.

This guidance is to enable organizations to consider alternative methods whilst maintaining basic control of documents.

The guidance is for organizations involved in the pharmaceutical lifecycle (Good Manufacturing Practices (GMP), Good Documentation Practices Practices (GDP), Good Laboratory Practices (GLP) studies regulated by the MHRA.

Existing electronic systems

Many companies already have validated systems that support electronic signatures on systems that are available remotely and If a company has these systems in place, then they should continue to use them.

Paper documents that were approved with wet ink signature

These are documents that have traditionally been printed on paper, physically handed to each reviewer in an office and approved using wet ink signatures.

Examples may include, but are not limited to:

• Validation protocols and reports
• Risk assessments
• Technical reports
• Quality management system documents that are paper-based such as SOPs, investigations, Deviations, Incident, Out of Specification and change controls.

These can be shared with remote workers, but they have no formal system describing how the review and approval can be recorded.

Alternative methods

The solution will vary between organizations depending on the type of document and the tools available to the person performing the approval e.g. printer, scanner/smart phone, secure email, third party software or existing systems that have tools to capture electronic signatures.

Principles to maintain Control

Regardless of what system or process is used, the following principles apply:

• Controls should be proportionate to the risk considering the type of document and the methods used for distribution and approval
• A signature performed remotely should be equivalent to the handwritten signature of the signatory
• The method of document distribution and approval should be defined to minimize the risk of error due to misunderstanding of what is being reviewed/approved

Risks involved in remote Approval

Aspects to consider when assessing risk include:

• How the approval signature is attributable to an individual
• Whether there is a legislative requirement or GxP guidance for a signature. If there is, then the signature should be considered more critical and have proportionately greater control – for example when a Qualified Person certifies a batch of finished product to enable release for sale
• The security of the electronic signature i.e. so that it can only be applied by the ‘owner’ of that signature
• How the act of ‘signing’ is recorded so that the document cannot be altered or manipulated without invalidating the signature or status of the entry
• Ensuring that all required associated data is available to a remote reviewer that would have been available to them if they were performing the review at a site

Some examples of issues with remote approval are included in Examples of issues with remote approval (PDF, 305KB, 4 pages).

Reference : https://www.gov.uk/guidance/approval-of-gxp-documents-when-working-from-home-during-the-coronavirus-covid-19-outbreak

Medicines and Health care products Regulatory agency (MHRA) are allowing alternative courses of actions for manufacturing or Quality control laboratory equipments or instruments during the outbreak.

During the corona virus pandemic it may not be possible for service personnel or external engineering support to operate as normal hence the following options are available to manufacturers and GxP laboratories.

If an engineer is available to attend site

A risk assessment should be performed to assess COVID-19 transmission risks in line with government advice.

Company health and safety procedures should be followed so the engineer can ensure social distancing and be supervised adequately during their time on site.

Calibration and maintenance protocols may be reviewed prior to the engineer visiting the site as per routine requirements, however, approval may be given electronically and Site visit documentation may also be signed electronically.

If an engineer cannot attend site but is available by either telephone or video call

A suitably trained employee may perform the calibration or maintenance task under the remote supervision from the engineer providing the site has all the required materials, parts and tools to perform the task.

The risks of this should be assessed and if required, the next maintenance or calibration task brought forward once current restrictions are lifted.

If an engineer is not available to attend site and remote supervision is not possible

A quality system record (e.g. change control or deviation) should be raised and the delay to the calibration or maintenance task should be risk assessed, considering;

• The criticality of the equipment and its intended use
• Frequency of the calibration/maintenance
• Whether it is an interim or annual recalibration/maintenance task
• Prior performance, including ‘drift’ between previous calibration or maintenance visits and recent breakdown history
• Performance checks that are performed on the equipment prior to use
• If alternative equipment is available to perform the task and is within its calibration/maintenance period

The risk assessment should also consider additional performance checks and verifications that should be performed to monitor the compliance status of the equipment.

The delay to a calibration or maintenance task should be documented and managed by the quality management system.

The documentation should be transparent to allow the person responsible for releasing product or making a regulatory claim of compliance to make a full and accurate assessment.

The calibration or maintenance task should be performed at the earliest when current restrictions on movement are removed and Equipment taken out of service following risk assessment should have outstanding maintenance or calibration work completed prior to being put back into use.

Off-site calibration/maintenance

There may be an option for controllable equipment to be shipped off-site for calibration or maintenance to be performed.

If this is not standard practice then the change should be assessed, detailing the risks of equipment leaving the site and the impact on the calibration or maintenance once the equipment has been returned and an assessment made as to whether it is fit for the intended use.

Substitution of laboratory equipment

Any analytical methods that may have been validated on a specific make/model of equipment may be transferred to an equivalent instrument after assessment of the impact on the validation status of the method.

If required, method validation may need to be performed to ensure the validity of the results generated.

Conclusion:

Each Pharmaceutical or Health care manufacturing and Quality control laboratory organization shall prepare the SOP for their respective sites for better compliance and it is required for domestic as well as regulatory Export markets.

Reference : https://www.gov.uk/guidance/guidance-for-manufacturers-and-good-practice-gxp-laboratories-on-exceptional-flexibilities-for-maintenance-and-calibration-during-the-coronavirus-co

Changes to products licensed by the US FDA are achieved via the provision of supplements to the original new drug application (NDA).

AR: Annual Report

Changes that can be submitted in an annual report are of a minor in nature and that have minimal potential to cause an adverse effect on the identity, strength, quality, purity, or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product.

 The affected product can be distributed at any time after the change has been internally approved and before the details are reported in the Annual Report.

At the end of a reporting period, any changes that have been implemented in the previous year are included together in a single notification to the agency.

CBE-0: Changes Being Effected 0

Changes classified as CBE-0 are minor (albeit moderate) changes to the product which can be implemented from when the FDA receives the supplemental new drug application (sNDA) application.

The product can also be distributed when the supplemental new drug application (sNDA) is received and CBE-0 changes are considered approved six months after receipt, if there are no technical issues raised by the FDA.

However, if the change is not approved then distribution must cease and a product recall may be required.

CBE-30: Changes Being Effected 30

Changes classified as CBE-30 are also deemed as minor (albeit moderate) and  Changes in this classification can be implemented and product distributed at risk, 30 days after the FDA receives the supplemental new drug application (sNDA), unless the FDA notifies the applicant otherwise.

Approval should be completed after six months, however, if the submission is rejected, a recall may also be required.

PAS: Prior Approval Supplements

This category covers major changes that are considered to have a substantial potential to adversely affect the identity, strength, quality, purity or potency of the drug product.

Product affected by these changes cannot be distributed until approval which should take up to four months, assuming there are no technical issues.