14-16 April 2021
A recent FDA warning letter (February 14, 2017) cites a lack of scientifically sound and appropriate sampling plans for inspection.
The warning letter clearly states that the Company has no scientific justification for the number of reserve samples selected for the yearly visual examination aimed at identifying any evidence of drug product deterioration. Similarly, the Company lacks appropriate statistical sampling plans for the inspection of paper label rolls.
Thus, this warning letter is a useful reminder of the regulatory need to sample a number of units (finished drug product, in-process materials, APIs, raw material, excipients, packaging components and labels) that is based on statistical criteria. Indeed, 21 CFR 211.84(b) requires that the number of containers to be sampled, and the amount of material to be taken from each container, shall be based upon appropriate criteria such as statistical criteria for component variability, confidence levels, and degree of precision desired, the past quality history of the supplier, and the quantity needed for analysis and reserve where required by 211.170.
Statistically-based sampling plans recognized by regulatory agencies are available (e.g. ISO 2859-1 or ANSI/ASQC Z1.4 for series of lots; e.g. ISO 2859-2 or ANSI/ASQC-Q3 for isolated lots) and presumably could be used for sampling the above mentioned reserve samples or rolls leaflets. In fact, one can classify the material to be sampled in three general categories:
1. Unitary material (it consists of essentially identical units e.g., finished product, leaflets, test tubes, vials, stoppers, medical devices etc.…)
2. Particulate material (Powders of API, Excipient, granulate, blend etc.…)
3. Bulky-continuous material (water, liquid solution, viscous solutions, gel, cream, compressed gas, steam etc.…)
The first category of material is easily amenable to statistical sampling by attributes. Sampling of the other two categories is often based on a risk-based approach aimed at multi-point sampling and testing to capture any intra-batch variability. At either category, the ultimate aim the sampling plan is to test/inspect a scientifically-sound selected representative sample.
Get more details in the FDA Warning Letter to Hospira Inc..