US Food and Drug Administration (FDA) will now insist the listing of new information related to drug product from pharma companies in their annual reports. This is part of the global regulatory authority’s Pharmaceutical Quality Initiative and its risk-based approach to chemistry, manufacturing, and controls (CMC) review.
In this regard, US FDA has released a draft guidance document regarding CMC post approval manufacturing changes reportable in annual reports.
According to the guidance issued by US FDA, after submitting a New Drug Application (NDA) or an Abbreviated New Drug Application (ANDA) and being granted approval from FDA, new drug applicants still have numerous post marketing regulatory responsibilities. Each year, within 60 days of the US approval, applicants must submit an annual report. This would cover topics on significant new information from the previous year that might affect the safety, effectiveness, or labelling of the drug product, distribution data and information regarding generic drugs, current labelling and any changes to such labelling, CMC changes, non-clinical laboratory studies, clinical data, status of post marketing studies and outstanding regulatory business.
All post approval CMC changes, beyond prior established variations documented in an NDA or ANDA are broken down into the categories of 'major,' 'moderate,' or 'minor.'
Each category of change is associated with different submission and implementation requirements. Major changes need to be submitted to FDA for prior approval before the product affected by the change may be distributed by the applicant.
Moderate changes would be required for submission at least 30 days before distribution, and in certain cases, at the time of distribution, stated Colleen Heisey, partner, Washington DC office of Hunton & Williams LLP in the firm's Food and Drug Practice in her report titled ‘CMC post approval manufacturing changes reportable in annual reports’.
For minor changes, the applicant may proceed with distribution and include the information regarding the minor change in the annual report, stated the guidance draft.
Specifically, the regulation specifies that minor changes related to alteration in the drug substance, drug product, production process, quality controls, equipment, or facilities that have a minimal potential to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product. This is because these factors might relate to the safety or effectiveness of the drug product.
For all changes, however, applicants must fulfill their regulatory requirement and assess how they affect product safety and efficacy, and demonstrate these effects through studies, allowing them to best determine whether it would be more appropriate to submit the change via supplement.
The draft guidance document on CMC post approval manufacturing changes that are reportable in annual reports targets the section of the regulations discussing minor changes to clarify for industry those FDA has determined “will likely present minimal potential to have adverse effects on product quality and, therefore, may be reported by applicants in the annual report,” stated Heisey.
Pharma companies in India stated that listed enterprises will need to adhere to the guidance issued by US FDA.