Pharmaceutical companies have continued to use traditional batch manufacturing—the process by which the components of a finished drug product are produced in groups (batches) that require several starts and stops rather than in a continuous stream—for decades with few changes. However, the FDA has become a strong advocate for continuous manufacturing— whereby production occurs in a highly automated, continuous flow without
interruption and with limited manual intervention—and it is gaining traction in the Pharmaceutical industry thanks to advances in technology and quality control.
From an information management perspective, batch and continuous manufacturing have different challenges and needs with regard to processes that should be followed in order to make the move from batch to continuous manufacturing. It is important for companies to be aware of the distinctions in order to stay compliant and make the right information available to the correct people.
1. Continuous Manufacturing Terminology - Knowledge Management Challenges
Most drug manufacturing is set up for batch processes so there will need to be an active move to continuous manufacturing. With regard to knowledge management, this means building up a base of continuous manufacturing information from different viewpoints such as the Business, Engineering/Manufacturing, Quality, and Regulatory that is easily searchable through classification based on taxonomies.
For example, the term “continuous manufacturing” is often used interchangeably with “continuous processing.” While there is no formal difference between the two, most industry experts make a distinction between them. Continuous processing is defined as one step of individual unit operations (blending, coating, milling, granulation, etc.) while continuous manufacturing is the process linked together from start (raw materials in) to finish (final product out). Continuous manufacturing is generally the preferred industry term but it is still common to see both. From a taxonomy perspective, it is important to be aware of the distinction and use of both terms in order to ensure the most relevant information is retrieved quickly.
Read the case study: Structuring Unstructured Content for Knowledge Management
There are few terms unique to continuous manufacturing as most concepts related to batch manufacturing are also used with continuous manufacturing. However, terms are sometimes used in a different context, especially with Unit Operations (i.e. “blending” vs. “continuous blending”). Continuous manufacturing terms should be incorporated into an overall drug manufacturing taxonomy to ensure the most relevant information is available to those who need it. This is key, since continuous manufacturing is still new to the pharmaceutical industry and many may need to familiarize themselves with topics such as specific continuous manufacturing equipment or unit operations in the continuous context (e.g., continuous coating of tablets).
2. Batch definition – Records Management and Quality Documentation Challenges
Batches and lots are harder to define in continuous manufacturing. The term “batch” refers to the quantity of material and does not specify the type of manufacturing. The FDA’s 21 CFR 210.3 defines a lot as “a batch, or a specific identified portion of a batch, having uniform character and quality within specified limits; or, in the case of a drug product produced by continuous process, it is a specific identified amount produced in a unit of time or quantity in a manner that assures its having uniform character and quality within specified limits.” Therefore, defining a batch is less obvious in continuous manufacturing, as it is possible to define a batch/lot at the product collection step by production time period, production variation (such as lots with different feedstock), or based on equipment cycling capabilities.
It is necessary to define a batch for the Documentation of Manufacturing required by FDA current good manufacturing practices (cGMP) covering batch production records and control records. As stated in 21 CFR 211.188: “Batch production and control records shall be prepared for each batch of drug product produced and shall include complete information relating to the production and control of each batch.” These records include documentation proving that each significant step in the manufacture, processing, packing, or holding of the batch was accomplished. Data integrity is vital, as these records must be checked for accuracy, dated, and signed.
The advantages look to outweigh the challenges as continuous manufacturing should play a larger role in the pharmaceutical industry in the near future. Be prepared to keep up with the information management requirements and knowledge management needs so that you can be on the cutting edge and reap the benefits of continuous manufacturing while remaining compliant.