In Industries, we always face confusion about the “Usage of expired Raw Materials” and “Retesting of expired raw materials” in the formulation of finished drug products. in this article, We will cover some Questions about Expired Raw and API materials in warehousing, as we have tried to explain them in a simple way.
- What is an Active Pharmaceutical Ingredient?
- Why use and regulate Active Ingredients?
- What is the Expiry Date?
- What is the Retest Date?
- Difference between an Expired API and a Retest Date?
- Can We use the Retest Date rather than the Expiry Date?
- Does the definition of expiry date in ICH Q7 preclude the rework or reprocessing of an expired API?
- Is it possible to extend the expiry date or retest date of the raw material?
- Can we use Expired API after Retest?
- When is it acceptable for an API manufacturer to extend an API retest date?
- Can expiration dates be extended?
- Is it Safe to the usage of Expired Raw Materials in Manufacturing that are near expiry?
What is an Active Pharmaceutical Ingredient?
Active pharmaceutical ingredients are synthesis chemicals or substances used in pharmaceuticals for pharmacological action, API mixed with other ingredients to for better withstand and absorption of finished drugs products. Such chemicals are designed to provide pharmacological activity or other direct impacts in medical diagnosis, cure, mitigation, treatment, or prevention, or to influence the structure and function of the body.
Why use and regulate Active Ingredients?
The quality of a drug’s active pharmaceutical components has a direct impact on its safety and efficacy. A drug without API is nothing and it will act as a placebo. In a number of events throughout the years, poorly made and contaminated active pharmaceutical substances have been linked to bad health results, including death. As a result, most nations throughout the world are currently regulating active substances. Active ingredient regulation will assist in improving the quality and safety of pharmaceuticals for consumers while also strengthening the pharmaceutical drug supply system.
What is the Expiry Date?
The expiry date of Active pharmaceutical ingredients is the date after which it can not be suggested to use. however it can be use used after the expiry date, but over time its efficacy may have decreased.
What is the Retest Date?
The retest date of active pharmaceutical ingredients (API) is a date by which an API is again sampled for retesting to ensure that it still meets the required specifications for the quality and safety of pharmaceutical products. Based on the self-life The retest date is set by the active pharmaceutical manufacturer. Retesting is effective before its expiry. retesting after the expiry date has no significance.
Difference between an Expired API and a Retest Date?
When it comes to expired APIs, there’s a lot of misinformation out there. To begin, an API, or active pharmaceutical ingredient, is a chemical that is used to manufacture a finished drug product.
An API can be utilized until it expires, but it cannot be used in pharmaceutical formulations after its expiry. The reason for this is that in order to be effective, an API must be pure. And once an API has been inactive for a time, it might begin to degrade and become less effective.
Can We use the Retest Date rather than the Expiry Date?
The expiry date and the retest date are completely different things. The expired API cannot be evaluated again for usage or manufactured products. Excipients used along with API can be retested, but API cannot be suggested to use after its expiration date, it can be retested within their self-life after API is manufactured. The retest date is done to ensure their expiration date.
Does the Definition of Expiry Date in ICH Q7 preclude the rework or reprocessing of an expired API?
According to the definition, the synthesis material should not be formulated after its expiry date. As per ICH Q7, the original intent of this definition was that expired API should not be used in drug products manufactured. Reprocessing [ICH Q7, 14.2] or reworking [ICH Q7, 14.3] the expired API may be permitted if the API manufacturer provides all applicable historical GMP documentation and stability data on the reworked or reprocessed API. In addition to GMP issues, there may be registration/filing considerations that are outside the purview of ICH Q7.
Is it possible to extend the Expiry Date or Retest Date of the raw material?
ICH Q7, says, it is out of scope for us if an API manufacturer is Manufacturing and labeling raw materials. As such, expiry dates, and retests are defined in ICH Q7. ICH Q7 also does not strictly apply to raw materials and may be used in a different manner by the raw material supplier. Expiry date, as defined in the glossary of [ICH Q7, 20], applies specifically to the API.
Based on an adequate scientific and risk-based explanation, API manufacturers may re-evaluate [ICH Q7, 7.5] and then utilize a raw material after the ‘expiry date’ or’ retest date’ (e.g., as per material attributes, testing, and stability). Similar explanations may be used to delay the re-evaluation of the contents. It is the API manufacturer’s role/responsibility to ensure that the raw materials are suitable for the intended application at the time of usage.
Can we use Expired API after Retest?
The misconception may be caused by the usage of the word “expiry” instead of “retest.” They are not similar.
If the API COA specifies a retest date, it can be utilized upon retesting (appropriate supporting stability data should be obtained). If the COA specifies an expiry date, it shall not be utilized in accordance with the ICH Q7 meaning of the word “expiry” as stated above.
The issue is that the term “expiry” is often used wrongly instead of “retest” on APIs. As per ICH, Q7 states that “Common practice for API is to use a retest date, not an expiration date,”. The term “expiry” refers to a time period after which the quality of the DS or DP cannot be insured. For example, stability data shows degradation after a certain time period. The term expiry is used when there is no intention of continuing the stability study to support a longer time period.
for example Assay Limit: NLT 99.5%, Degradation Limit: MNT 1.0%, If this API has a 3-year expiration date and just one month remains before it expires.
If the results of the retest are Assay = 99.8% and Degradation products = 0.88%
In such cases, we cannot use it in the manufacture of a product with a 2-year expiry date since the API will fail to satisfy the standards for the next two years.
In the example, we will use an excessive amount of API to make its assay 100% in the finished product, resulting in its assay having no value in completed items. Its degradation products will be diluted in the final product before it is tested for a new impurity specification. As a result, it will be pointless in the finished doses.
As a consequence, we don’t have to worry about the quality of the API in the finished doses; instead, we have to make sure that the finished product matches its specifications. If you are using a raw API material that is about to expire, you must have adequate scientific evidence to verify that it will fulfill the specifications for the whole shelf life of the finished dosage product.
When is it acceptable for an API manufacturer to extend an API Retest Date?
A retest date is used to check that the API is still appropriate for usage. Based on strong science and long-term stability data for that API, as well as testing of the particular batch that has been stored according to label conditions, the API producer may extend the retest date of a single batch. In some areas, regulatory authority permission for the batch’s retest date extension may be necessary.
If an API manufacturer wishes to modify (i.e., extend) the retest date for future batches of an API, it must do adequate stability testing to justify the change and submit the new retest date and accompanying data in a regulatory filing as specified by regional standards.
Can Expiration Dates be extended?
According to the FDA’s industry guidance, “Changes to an Approved NDA or ANDA,” the manufacturer of an approved drug product may extend the expiration date based on its own testing and adequate data in conformity with a protocol approved in the new drug application (NDA) or abbreviated new drug application (ANDA) (see 21 CFR 314.70). To assist in helping medicine shortages, the FDA has authorized expiry date extensions where data supporting the extension is available.
Is it Safe to the usage of Expired Raw Materials in Manufacturing that are near expiry?
FDA, WHO, and ICH guidelines do not state that Raw components that are about to expire cannot be used in the formulation. Some guidelines suggest retesting near-expired raw materials, but only for API suppliers. But Yes, You can utilize the API a few days before manufacturing the finished product as long as the resulting dosage form is stable during its shelf life. To determine the expiry date, apply the TGA/DSC method. Furthermore, for safe API usage, the amount of the limit of extra components given in the official monograph must be assessed.
To begin, you must confirm that API is still as per assay requirements For some raw materials that have reached their expiration date, you must retest them.
If the assay is still within the criteria (see the monograph instead of the references such as USP/BP/EP) you may use those raw materials for the production/manufacturing process.
However, we must employ it with caution because passing results in an API retest are insufficient to include it in the formulation. The assay and degradation products primarily determine the expiration of any API. If both are within the limit, the API can be used in the formulation. However, if any of these values are near the limit, they should not be used in the formulation. Industries sometimes employ API a few days before it expires to create a product with a two or three-year expiration date.
Conclusion
For companies lacking regulatory guidelines, the Usage of Expired Raw Materials or near-expired materials in drug formulation remains a major problem. Based on precise stability and risk management data, industries continue to use near-expiry and expired raw materials.
We can use API with near-limit results since API results have no significance after formulation and produced items must only conform to its specifications. This is why there are no guidelines. API must be acceptable only when it is employed in the formulation.
Furthermore, several sectors employ the concept of 100% potency value while administering API. Even after the pharmaceutical product has been produced, it is subjected to stability testing until it reaches its expiration date.
Reference:
FDA 21 CFR
-
by
-
