Regulatory Open Forum

Hello RegEx,

I had a colleague pose a question of curiosity regarding how tightly IP must be reconciled at a distribution site. She has primarily worked in QA overseeing manufacturing/GMP from the Sponsor side, but has not dealt with distribution from the Sponsor side. It is our assumption that IP coming out of a distribution facility must be 100% reconciled (which would typically be the case for a manufacturing facility), but we were curious, if it is not 100%, what that percentage might be? This question came up because, for a larger company, there may be thousands of units at a distributor - what level of accountability must be achieved? Taking this a step further from the distributor to the clinical site - would be correct to assume a clinical site must maintain 100% accountability of IP product?

Finally, does the level of reconciliation vary based on IP type (device/drug/biologic), risk classification, etc.? If there is any regs/guidance covering these questions that would be interesting to see.

For the purpose of this exercise, this would primarily be for operations conducted in the US, but we would also be curious if there were any regs/guidance elsewhere.

Thank you kindly reg community!

100% accountability of IP at all locations is expected.

21 CFR 312.53(b) states that a sponsor shall ship investigational new drugs only to investigators participating in the investigation. 312.57(a) states that a sponsor shall maintain adequate records showing the receipt, shipment, or other disposition of the investigational drug. These records are required to include, as appropriate, the name of the investigator to whom the drug is shipped, and the date, quantity, and batch or code mark of each such shipment.

312.59 states that the sponsor shall assure the return of all unused supplies of the investigational drug from each individual investigator whose participation in the investigation is discontinued or terminated. The sponsor may authorize alternative disposition of unused supplies of the investigational drug provided this alternative disposition does not expose humans to risks from the drug. The sponsor shall maintain written records of any disposition of the drug in accordance with § 312.57.

312.62 states an investigator is required to maintain adequate records of the disposition of the drug, including dates, quantity, and use by subjects. If the investigation is terminated, suspended, discontinued, or completed, the investigator shall return the unused supplies of the drug to the sponsor, or otherwise provide for disposition of the unused supplies of the drug under § 312.59.

Anytime you see a regulation that includes the term "shall", you can believe that there are no exceptions. To understand how seriously FDA takes this, a recent example was that an investigator outside the US shipped IP kits back to the distributor at the end of the study, including unused IP and any empty bottles. One empty bottle was not included in the investigator reconciliation list and was considered by the FDA inspector a serious compliance violation.

Hello RegEx,

I had a colleague pose a question of curiosity regarding how tightly IP must be reconciled at a distribution site. She has primarily worked in QA overseeing manufacturing/GMP from the Sponsor side, but has not dealt with distribution from the Sponsor side. It is our assumption that IP coming out of a distribution facility must be 100% reconciled (which would typically be the case for a manufacturing facility), but we were curious, if it is not 100%, what that percentage might be? This question came up because, for a larger company, there may be thousands of units at a distributor - what level of accountability must be achieved? Taking this a step further from the distributor to the clinical site - would be correct to assume a clinical site must maintain 100% accountability of IP product?

Finally, does the level of reconciliation vary based on IP type (device/drug/biologic), risk classification, etc.? If there is any regs/guidance covering these questions that would be interesting to see.

For the purpose of this exercise, this would primarily be for operations conducted in the US, but we would also be curious if there were any regs/guidance elsewhere.

Thank you kindly reg community!