why two different batches key starting material can't be mixed to produce active Pharmaceutical Ingredient

Mixing batches of starting materials to produce an active pharmaceutical ingredient (API) is generally not recommended for the following reasons:

1. **Traceability**: Each batch of starting material has its own unique history, including the source, manufacturing process, and quality control testing. Mixing batches makes it difficult to trace the origin of the API back to the individual starting material batches, which is important for regulatory compliance[2].

2. **Consistency**: Combining batches with potentially different properties, such as particle size, density, or impurity profile, can lead to inconsistencies in the final API. This can impact the quality, safety, and efficacy of the drug product[1][3].

3. **Contamination**: There is a risk of cross-contamination when mixing batches, especially if the starting materials have different grades or are used for different products. This can compromise the purity of the API[2].

4. **Regulatory requirements**: Regulatory guidelines, such as the FDA's Q7A Good Manufacturing Practice (GMP) guidance, recommend against mixing batches of starting materials for API production. The guidance states that "in-process mixing of fractions from single batches is generally acceptable, but combining fractions from different batches is not considered acceptable practice"[2].

In summary, while it may be tempting to mix batches of starting materials to save time or resources, the potential risks to product quality, consistency, and regulatory compliance outweigh any potential benefits. It is best to process each batch of starting material separately to ensure the highest quality and safety of the final API.

Citations:

[1] Batch versus continuous blending of binary and ternary pharmaceutical ... https://www.sciencedirect.com/science/article/pii/S2590156721000402

[2] Guidance for Industry, Q7A Good Manufacturing Practice ... - FDA https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-q7a-good-manufacturing-practice-guidance-active-pharmaceutical-ingredients

[3] Batch versus continuous blending of binary and ternary pharmaceutical ... https://www.pharmaexcipients.com/continuous-manufacturing/batch-versus-continuous-blending/

[4] 3 Critical Things for Dry Blending Process in Pharmaceutical Industry https://www.customprocessingservices.com/blog/critical-things-to-know-about-pharmaceutical-blending-process

[5] Impact of excipients on batch and continuous powder blending https://www.sciencedirect.com/science/article/pii/S0032591021001170