CDER Guidance Documents

Proper utilization will be helpful in gathering information on product stability and leading to an optimized formulation. API stability must also be determined in final forum as it is necessary to ensure efficacy and safety of the finished product. Testing procedures must include a stability indicating test which will distinguish the active ingredient from any degradation products and be able to make a reliable estimate of the quantity of any degradate. The stability indicating test does not have to be the assay method used to determine product strength. Impurities and Degradates Impurities are chemicals or solvents incorporated into a raw material during production. The level of impurities does not typically change over time. Controlling the product process can minimize impurities. By monitoring impurities, the impact on raw material can be determined. Degradates are formed by component breakdown.


Due to the lot-to-lot variability, the stability and quality of extended drug products can only be assured by periodic testing and systematic evaluation of each lot. The results of this stability program can only be related to products that have been carefully stored in their original sealed container closures. How often have you been in the field, deployment, etc. Well, do you know how this redistribution affects the expiration date?

Guidance for Industry Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products For questions on the content of the.

FDA, set out to investigate the efficacy of pharmaceutical drug stockpiles beyond their expiration dates. The results showed that about 90 percent of the drugs were still effective far past their expiration dates. Fifteen years ago, the U. Sitting on a one billion dollar stockpile of drugs and facing the daunting process of destroying and replacing its supply every two to three years, the military began a testing program to see if it could extend the life of its inventory.

The testing, conducted by the U. Food and Drug Administration, ultimately covered more than drugs, prescription and over-the-counter. The results, never before reported, show that about 90 percent of them were safe and effective far past their original expiration date, at least one for 15 years past it. In light of these results, a former director of the testing program, Francis Flaherty, says he has concluded that expiration dates put on by manufacturers typically have no bearing on whether a drug is usable for longer.

Flaherty notes that a drug maker is required to prove only that a drug is still good on whatever expiration date the company chooses to set. The expiration date doesn’t mean, or even suggest, that the drug will stop being effective after that, nor that it will become harmful. Marketing Issue “Manufacturers put expiration dates on for marketing, rather than scientific, reasons,” says Mr. Flaherty, a pharmacist at the FDA until his retirement last year.

Benefits of FDA Approved Products

Received Jun 15; Accepted Jun 8. Such comprehensive and common language is currently lacking from various guidelines, which confuses implementation and impedes comparisons of different methodologies. The five new terms that are necessary for a coherent discussion of shelf life are:

shall bear an expiration date determined by appropriate stability testing described in (b) Expiration dates shall be related to any storage conditions both the reconstituted and unreconstituted drug products. (d) Expiration dates shall appear on labeling in accordance with this section shall not be enforced for human OTC drug.

Background[ edit ] Shelf life is the recommended maximum time for which products or fresh harvested produce can be stored, during which the defined quality of a specified proportion of the goods remains acceptable under expected or specified conditions of distribution, storage and display. If the cans look okay, they are safe to use. Discard cans that are dented, rusted, or swollen. High-acid canned foods tomatoes, fruits will keep their best quality for 12 to 18 months; low-acid canned foods meats, vegetables for 2 to 5 years.

Most food is still edible after the expiration date. In most food stores, waste is minimized by using stock rotation , which involves moving products with the earliest sell by date from the warehouse to the sales area, and then to the front of the shelf, so that most shoppers will pick them up first and thus they are likely to be sold before the end of their shelf life.

This is important, as consumers enjoy fresher goods, and furthermore some stores can be fined for selling out of date products; most if not all would have to mark such products down as wasted , resulting in a financial loss. Shelf life depends on the degradation mechanism of the specific product. Most can be influenced by several factors: Product quality is often mathematically modelled around a parameter concentration of a chemical compound, a microbiological index, or moisture content.

Bacterial contaminants are ubiquitous, and foods left unused too long will often be contaminated by substantial amounts of bacterial colonies and become dangerous to eat, leading to food poisoning. However, shelf life alone is not an accurate indicator of how long the food can safely be stored. For example, pasteurized milk can remain fresh for five days after its sell-by date if it is refrigerated properly. However, improper storage of milk may result in bacterial contamination or spoilage before the expiration date.

Antibiotics and Expiration Dates

Following is a list of commonly used GMP terms Acceptance criteria: The accuracy of an analytical procedure expresses the closeness of agreement between the value which is accepted either as a conventional true value or an accepted reference value and the value found. This is sometimes termed trueness. The degree of closeness of the determined value to the nominal or known true value under prescribed conditions. The accuracy of an analytical method is the closeness of test results obtained by that method to the true value.

Accuracy can often be expressed as percent recovery by the assay of known, added amounts of analyte.

Federal Shelf Life Extension Program Fact Sheet Overview. The federal Shelf Life Extension Program (SLEP) extends the expiration dates on qualifying drugs and other materiel in federal stockpiles. SLEP is administered by the U.S. Department of Defense (DoD) in cooperation with the U.S. Food and Drug Administration (FDA). 1 The program is an acknowledgement that the actual shelf life .

Formulation basis should meet the following criteria; and its title, edition, year of publication and page numbers should all be indicated. A photocopy of complete reference pages should be provided. If the reference is in neither Chinese nor English, a word for word Chinese translation should be provided; but proper names or technical terms can be listed in English. Extra pharmacopoeia, which is not an official reference book, is for reference only.

If the applied formula is not completely consistent with the submitted reference and some alternations have been made, a statement explaining the alternation should be provided. Information in relation to the actual changes should be submitted as appropriate. Tablets, film-coated tablets and sugar-coated tablets can use the same formulation basis, but not for enteric-coated tablets. The formulation basis of ointment and cream can be used interchangeably, provided that the products are not under pharmacovigilance.

If the formulation basis or the CPP is of tablets, the reasons for the application of double-layered tablets should be given.

FDA issues final rule on combination products cGMPs

A simple, rapid, reverse phase and stability-indicating high-performance liquid chromatography HPLC method for the estimation of imatinib in solution and in plasma under forced degradation conditions was developed. The method was validated in solution as well as in plasma, and the response was found to be linear in the concentration range of 0. Forced degradation studies revealed that imatinib undergoes degradation under different stress conditions.

The developed HPLC method could effectively resolve degradation product peaks from imatinib except at neutral pH. Further, no interference was found at the retention time of imatinib from any plasma components, indicating selectivity of the developed method.

FDA Laws & Pharmacy Practice USFDA Compliance Policy Guide CPG Lack of expiration date of stability data 26 Expiration Date 3 21CFR Expiration Dating (excerpts) (e) Homeopathic drug products are exempt human OTC drug products if their labeling does not bear.

You will find in this section the latest medical thoughts expressed by the experts themselves which we feel are of national importance to all folks. No opinions expressed were written by this civilian editor. Note – FDA is a patriotic institution. FDA announces comprehensive regulatory plan to shift trajectory of tobacco-related disease, death The U.

Food and Drug Administration today announced a new comprehensive plan for tobacco and nicotine regulation that will serve as a multi-year roadmap to better protect kids and significantly reduce tobacco-related disease and death. The goal is to ensure that the FDA has the proper scientific and regulatory foundation to efficiently and effectively implement the Family Smoking Prevention and Tobacco Control Act. The agency will also seek input on critical public health issues such as the role of flavors in tobacco products.

Tobacco use remains the leading cause of preventable disease and death in the United States, causing more than , deaths every single year. The agency intends to issue an Advance Notice of Proposed Rulemaking ANPRM to seek input on the potential public health benefits and any possible adverse effects of lowering nicotine in cigarettes. Because almost 90 percent of adult smokers started smoking before the age of 18 and nearly 2, youth smoke their first cigarette every day in the U.

To be successful all of these steps must be done in concert and not in isolation.


Drug expiration dates are meant to indicate the date at which the drug’s potency begins to diminish. The closed-container environment must vating the containers the drugs are bought and sold in. The purpose of this expiration date is to inform consumers about the potency and effectiveness of the drug at the time of purchase. The tests also mimic the ideal storage areas the drug should be placed in, usually a cool, dry area.

Section (e) of the CGMP regulations states that the accuracy, sensitivity, specificity, and reproducibility of test methods shall be established and documented (21 CFR (e)).

Pfizer Introduction From a pharmaceutical development point of view, stability studies are frequently on the critical path to starting patient studies and registration stability studies, as described in the International Conference on Harmonisation ICH guideline Q1A R2 , are commonly the activity on the critical path to regulatory filing and approval [1].

Stability studies are also a significant resource commitment in both pre and post-approval phases. This article examines the decisions to be made regarding the design of a stability strategy during development and some alternative approaches, compared to those traditionally followed, are proposed as being more scientifically rigorous.

Following these approaches would lead to better product understanding and robustness as well as to a reduction in the number of scientifically redundant stability studies. Traditional stability studies overview The development of the ICH stability guidelines led to a significant degree of harmonization of expectations and, more recently, the World Health Organization WHO stability guideline has extended the reach of these efforts [2,3]. However, although the guidelines state that alternative approaches can be used when scientifically justified, pharmaceutical companies may be reluctant to propose any significantly different approaches when subsequent long delays may be incurred to a development program if a regulatory body refuses to accept the alternative approach followed.

Additionally, in some regions details from the ICH guidelines have been either written into, or are referred to in, local regulations [4,5]. The first stability studies performed are usually forced degradation studies [1]. These are carried out to understand the primary degradation products of the molecule and to aid analytical method development stability-indicating methods to be subsequently used during long-term stability studies.

Long-term stability studies will also be initiated on both the active pharmaceutical ingredient API and the drug product, generally following many of the principles contained in the ICH stability guidelines, with storage at accelerated and long-term conditions. Unless the expectations outlined in ICH guideline Q1A R2 have been met as part of the clinical stability program, registration stability studies are traditionally performed before filing a Common Technical Document CTD.

Q1A R2 also states that if the registration stability batches are not made at commercial scale, then the first three commercial batches need to be placed on stability. Furthermore, after this point batches are usually placed on stability annually, an expectation which has been included in the WHO stability guideline [3]. In addition, when changes are made e.


Labeling and packaging materials shall be representatively sampled, and examined or tested upon receipt and before use in packaging or labeling of a drug product. Any labeling or packaging materials that do not meet such specifications shall be rejected to prevent their use in operations for which they are unsuitable. Access to the storage area shall be limited to authorized personnel.

Adequan ® i.m. is the ONLY FDA approved equine polysulfated glycosaminoglycan (PSGAG) for the intramuscular treatment of non-infectious degenerative joint .

Supportive Stability Data Number and Size of Batches Initial stability testing by accelerated testing may be performed on a batch smaller than the normal production size as long as the batch is produced by similar equipment as would be used for regular production. Generally, the placing of three initial batches into the long term stability program is considered minimal to assure batch uniformity for establishing an expiration date.

Since a dosage form is a complex unit and there are continued variables in the production process, such as change in personnel, raw material lots and suppliers, and equipment, it is imperative that stability studies are not limited only to initial production batches but a portion of annual production batches be the subject of an ongoing stability program. Accelerated Studies When accelerated stability studies are performed, one batch may be adequate in order to establish a tentative expiration date.

This is acceptable since it is not the purpose of an accelerated test to determine batch uniformity but rather to test for kinetic degradation. The use of accelerated testing data to establish a tentative expiration dating period of greater than three years is discouraged when it is based solely on accelerated data. Combining data compiled at room temperature and at accelerated temperature is possible to justify an expiration dating period of over two years.

This can be done, as an example, by taking a sample product that has been at room temperature for one year and subjecting that sample to accelerated temperature conditions. The expiration dating period used would then be the sum of that justified individually at each storage condition.