Month: November 2021

Guidelines for Pharmaceutical Stability Study

Definition :

What is stability studies

The ability of a pharmaceutical product to retain its physical and chemical properties within specified limits throughout its shelf life.

Types of Stability Studies :

Long term testing

Stability studies under the recommended storage condition for the re-test period or shelf life proposed (or approved) for labeling.

Intermediate testing

Studies conducted at 30°C/65% RH and designed to moderately increase the rate of chemical degradation or physical changes for a drug substance or drug product intended to be stored long term at 25°C.

Accelerated testing

Studies designed to increase the rate of chemical degradation or physical change of a drug substance or drug product by using exaggerated storage conditions as part of the formal stability studies. Data from these studies, in addition to long term stability studies, can be used to assess longer term chemical   effects at non-accelerated conditions and to evaluate the effect of short term excursions outside the label storage conditions such as might occur during shipping. Results from accelerated testing studies are not always predictive of physical changes.

Climatic zones The four zones in the world that are distinguished by their characteristic prevalent annual climatic conditions.

Climatic Zone No.DefinitionStorage ConditionAreas covered under the zone
ITemperate climate21°C & 45% RH.United     Kingdom,      Northern                Europe, Canada, Russia, United states, Japan etc.
  IISubtropical and Mediterranean climate25°C/60% RHUnited   States,   Japan,  Southern Europe (Portugal-Greece) etc.
IIIHot & dry climate30°C/35% RHAustralia, Argentina, Egypt, Iran, Iraq, Sudan, India etc.
  IVAHot & humid climate  30°C/65%Brazil,     Ghana,     Indonesia,               Nicaragua, Srilanka, Vietnam, Philippines, Uganda, Thailand, India etc.
IVBHot & very humid climate30°C/75%Brazil, Asian countries etc.

Factors affecting stability of the product


The rate of chemical reaction increases exponentially for each 10°C increase in temperature. This relationship has been observed for nearly all drug hydrolysis and some drug oxidation reaction.


Exposure to primarily, UV illumination may cause oxidation (photo oxidation) and scission (Photolysis) of covalent bonds.


Presence of oxygen, nitrogen.

Humidity (Moisture):

Esters & beta-lactoms are the chemical bonds that are most likely to hydrolyze in the presence of water.

E.g. the acetyl ester in aspirin is hydrolyzed to acetic acid and salicylic acid in the presence of moisture, but in a dry environment the hydrolysis of aspirin is negligible.

Selection of Batches

For new drug product, samples of at least three consecutive validation batches shall be kept for accelerated, Intermediate and long-term stability.

For routine stability study, one commercial batch shall be kept for long term stability on every year.

Testing frequency

Testing frequency shall be determined based on condition at which stability is performed.


Accelerated stability shall be conducted at 0, 3 and 6 months.

Long term

Long-term stability studies shall be carried out at the intervals of, Every three months on first year 0, 3, 6,9,12,

Every six months on second year 12, 18, 24

Every year thereafter through the proposed shelf life 24, 36, 48 and 60

Eg: 0, 3,6,9,12,18,24,36,48 and 60 months.

Intermediate Intermediate stability studies (minimum four time points, including initial and final points) shall be carried out at 0,3,6,9 and 12 months or up to 60 months.

Sampling for Stability Study

QA shall inform to QC regarding type of stability study to be performed. QC shall calculate the sample quantity and shall inform to QA.

Total sample quantity per batch shall be equivalent to 1.5 times of the quantity required for single complete or partial analysis & based on number of stations plus additional one station (since stability testing has to be continued for 12 month beyond the expiry).

Incubation of Stability Samples and Storage conditions

Samples shall be incubated as per below guideline.

Identify the storage conditions based on the Pharmacopoeial data or literature information or R&D information. For add on batch use long term storage conditions.

The long term testing shall cover a minimum of 12 months’ duration on at least three validation batches at the time of submission and shall be continued for a period of time sufficient to cover the proposed shelf life.

Long term, accelerated, and, where appropriate, intermediate storage conditions for drug products are detailed in the sections below.

StudyStorage conditionMinimum time period covered by data at submission
  Long term25°C ± 2°C / 60% RH ± 5% RH or 30°C ± 2°C / 65% RH ± 5% RH 12 months
Intermediate*30°C ± 2°C / 65% RH ± 5% RH6 months
Accelerated40°C ± 2°C / 75% RH ± 5% RH6 months

* If 30°C ± 2°C / 65% RH ± 5% RH is the long-term condition, there is no intermediate condition.

If long-term studies are conducted at 25°C ± 2°C/60% RH ± 5% RH and “significant change” occurs at any time during 6 months’ testing at the accelerated storage condition, additional testing at the intermediate storage condition should be conducted and evaluated against significant change criteria.

The initial application should include a minimum of 6 months’ data from a 12-month study at the intermediate storage condition. Temperature & Humidity of stability incubator shall be monitored on daily basis. If incubation of the stability samples is delayed by 30 days or more from the release date of the batch, initial (0 month) analysis shall be performed again before incubation.

Analysis of the sample shall be performed on the due date or if not possible, then  complete within  below tolerance limit from due date.

Sr. No.Stability StationTolerance (From due date of analysis)
  1.1M , 2M, 3M Accelerated, 3M long term, 3M Intermediate term  ± 07 days
  2.6M Accelerated 6M, 9M, 12M long term. 6M, 9M, 12M Intermediate term.  ± 15 days
3.18M & onwards of long term.± 30 days

If there is any out of trend result or failure to meet specification (significant change)  in  stability analysis, results shall be intimated to Head – QC.

Head – QC or designee shall investigate the out of trend (OOT) results according to the OOT SOP .

In case of Changes in the manufacturing process or site:

If minor changes done in the manufacturing process, Sample from batches produced under each change shall be added to stability program (one batch).

If major changes done in the manufacturing process, collect the samples from the new batches (three batches) and perform the stability like new product. In such a case the protocol and report procedure number shall be changed.

In case of manufacturing site change, evaluate the affect on stability of the drug product by keeping one batch for stability.

Stability guideline :

ICH guideline: ICH Q1A (R2)

Orange guide

Vendor Management System in Pharmaceutical Industry


New Vendor: Manufacturer identified by Formulation Development or purchase department as a manufacturer to supply of a specific material from a specific manufacturing site.

Approved Vendor: Manufacturer of raw material, primary and printed packaging material, which has been approved by QA to supply a specific material from specific site, based on the satisfactory cGMP history as well as compliance of material to specification.



The requirement of new raw & packing materials and their profiles shall be given by the formulations development department.

In charge-purchase (Vendor development) shall identify the vendors with the available  information based on specifications provided by formulations development department.



In order to select a new vendor, evaluation of the manufacturer’s capability, service performance and quality history is required. Purchase department shall collect and maintain information of the new  vendor through the vendor registration form for manufacturer and for supplier or Trade.

Purchase department will get technical information regarding the material through vendor questionnaire from the vendor which includes the brief manufacturing process, TSE/BSE free declaration, impurity profile, residual solvent information, GMO free declaration, Melamine free declaration, Gluten free declaration and stability data/shelf life statement etc. as applicable depending upon the type of material.

GMO : Genetically Modified Organism

Note: For non-critical excipients requirement of impurity profile, residual solvent information, stability data, GMO/Melamine/Gluten free declarations are not mandatory.

Purchase department shall ask the vendor for analytical method and analytical method  validation data for the materials claiming residual solvents. Based on the evaluation of above information and vendor registration form, Purchase/Formulation development department shall ensure that vendor is ready to supply material of required grade with specific requirement, if any.

Purchase department shall ask the vendor for pre-purchase samples of at least one batch depending    upon the along with its certificate of analysis and shall be sent to Formulation Development and/or Quality Control for analysis.

Formulation Development and/or Quality Control shall evaluate the source material lots and on compliance of the sample as per specification and shall confirm the suitability as per specification to purchase department.

Formulation Development and/Quality Control will intimate the purchase and QA for suitability of sample.

Based on the assessment report from Formulation Development and/Quality Control satisfactory evaluation of data provided by the vendor, the new vendor shall be considered as a ‘Temporary Approved’.

The vendor list contains Material Code, Material Name, Synonym/ Storage Condition, Manufacturer Name and Site Address, Suppliers Name and Address and current approval status. The vendor list shall be prepared, reviewed and approved. A separate vendor list shall be prepared for US/UK market and others.

Once vendor is temporary approved, vendor code is to be assigned to the particular vendor as well as material code in SAP is to be generated by purchase department in co-ordination with SAP department.


Temporary approved” vendor becomes “Approved” vendor if following conditions are met-

For Manufacturer

Another Two commercial lots supplied by Temporary approved vendors are analysed and passed.

In case of API/ Primary packing material, vendor questionnaire is filled and vendor audit is done and complied.

In case of excipients and secondary packing material questionnaire is  completed.(if required, audit to   be carried out)

When manufacturing site audit is required, it shall be carried out by site QA/CQA to assess compliance with cGMP requirements.

The manufacturing site of the vendor shall be audited as per the checklist.

Based on the audit findings, a detailed report shall be classified as critical(C), Major (M) and minor (N) as described under definitions.

The purchase department shall send the site audit report prepared by site QA/CQA to the vendor. The vendor should respond in a period of 30 days after receipt of the audit report from purchase department.

The audit compliance report received from the new vendor shall be evaluated by the audit team members and recommendations shall be given to approve or reject the vendor by head QA.

Re-audit may be required for ensuring compliance in case of critical deficiencies observed during the audit.

QA shall update the vendor list once in 6 months to include or exclude approved vendor and to reflect the change in the status of vendors.


For approved vendor’s evaluation, following steps shall be followed:

Evaluation of the vendor’s quality performance shall be done once in a year. This annual evaluation

shall include review of rejection rate of the vendor’s lots and resolution of quality issues, if any

Yearly trending of all API from the Vendor shall be carried out of quality issues, if any.

Reassessment of quality systems shall be carried out if the rejection rate on quality grounds is higher than 20%.

All the vendor’s of API and primary packing materials shall be audited once in three years.

The vendor should respond with audit compliance report in a period of 30 days after receiving the audit report from purchase department.

If the compliance is not satisfactory, then the vendor rating will be downgraded or disapproved and deleted from the list. QA will update the vendor list accordingly and communication of the same shall  be sent to QC, warehouse and purchase department.


Vendors failing to meet the GMP requirements and those consistently (up to three lots) failing to meet quality standards shall be disqualified and blocked for supply of material by QA. However vendor can immediately be disqualified, Incase of any critical failure e.g. failing in potency (Assay below 80 %), microbial test (failure in pathogens). If the satisfactory corrective actions are taken by the vendor to resolve the quality problems and non- compliances, the vendor shall be re-approved for the supply.


Quality Management System (QMS)Importance in Pharmaceutical Industry

What is Quality Management system :

A Quality management system (QMS) is the core of any quality and compliance process. It is a regulatory requirement that the Food and Drug Administration (FDA) and other global regulatory bodies consider critical. An automated QMS system reduces audit time and findings and lowers the risk of product recalls. It improves product quality and safety, increases customer satisfaction and ensures FDA and ISO compliance.

Pharmaceutical Quality professionals are facing more challenges, and have more opportunities to improve quality and compliance than ever before. Mergers and acquisitions, complex supply chains, data integrity issues, and tightening regulations are all forces that affect pharmaceutical quality strategies and processes on a day-to-day basis. Plus, the FDA and other regulatory bodies are increasingly focused not only on compliance, but on the importance of building a culture of Quality management in the pharmaceutical industry.

An effective pharmaceutical Quality management system (QMS) will help you develop a culture of quality, support data integrity, keep suppliers under control, and maintain overall compliance. QMS data must also be structured to drive consistent metrics, risk calculations, and other trend analysis.

What is the Purpose of Quality Management system :

AQ management system can be defined as a collection of business processes that are focused on meeting customer requirements on a consistent basis. This may seem simple enough, however, it is essential that certain obstacles are overcome for your QMS to be successful.

With this in mind, ask yourself the following questions:

  • Do the same mistakes keep on being repeated?
  • Is there lack of visibility between each of your departments?
  • Do you have a high customer churn rate, negative customer reviews or perhaps a declining bottom line?

If you answered yes to any of the above, it may be that your QMS is not working as it should be.

The purpose of a quality management system is to ensure every time a process is performed, the same information, methods, skills and controls are used and applied in a consistent manner. If there are process issues or opportunities, this is then fed into the quality management system to ensure continuous improvement.

Importance of Quality Management System:

Here are reasons why quality management systems are so important for pharmaceutical companies:

Lessen the Risk of Errors :

The most obvious reason to invest in a QMS is to assist your company to reduce errors made when producing products. Without an advanced system where all employees involved understand their roles and responsibilities and communicate with each other, there will be more chance that errors will be made. Pharmaceutical companies of all sizes are at risk of doing mistakes without QMS in place. With an advanced QMS in place, everyone understands the tasks they need while completing a project. And, what steps ought to be taken each time to lessen the risk of errors from occurring.

Cut Costs with Quality Management System :

Errors can result in the wastage of products and money for your company. Not only are you wasting money on scraping products with errors that don’t meet the standards they require, but also you are wasting your employee’s time. Redo the work because of errors takes time far from other important tasks that still ought to be complete. As an advanced QMS, it streamlines production, makes it more efficient, and helps everyone involved become more productive. Also, companies may be able to see an increase in profits as well.

Encourage you to Constantly Upgrade :

Implementing an advanced QMS is a great place to begin, but the work doesn’t end there. The current system which you are using is unlikely to remain consistent, which is really a good thing. A quality management system encourages companies to keep them updated to improve their operations and makes it easier to identify areas where you ought to change. Technologies may also change, requiring you to adapt and upgrade your system to run more smoothly.

Customer Satisfaction :

Improving your company’s efficiency and production process are huge benefits to having an advanced QMS in place. However, the foremost important goal of all pharmaceutical companies is to make products that will help customers to live better. Ensuring that you’re producing high-quality products that are thoroughly checked over throughout the whole production process means you’re delivering better products to your customers. Customer satisfaction is more important for the companies, as they give your company positive reviews, which leads to increase sales.