Lean Documentation 4

Manufacturing Instructions and Records

Operators are expected to follow manufacturing instructions to produce a product that meets the required specification.  Typically these instructions will be written by technical experts, the chemical engineers who were responsible for the technology transfer, the process validation and so on.  They may be comprehensive and detailed, but that doesn’t make them good.

Manufacturing process instructions (MPIs) are often written in combination with the corresponding report, the manufacturing process record (MPR), so that operators follow an instruction then record the outcome in the same document.  This combined protocol/report works well in some respects, but it can result in very large, unwieldy documents.

The problems I commonly see with MPIs and MPRs, whether separate or combined, and the impact these have on the business, are as follows:

Let’s look at some of these in more detail:

Document is too detailed/Too much data is recorded

While it’s true that operators require a certain amount of information to be able to do their job effectively (Eudralex Volume 4 guidelines specify ‘detailed production instructions’), it’s also true that providing a lot of information can make it more difficult for them to find the information they require.  In addition, the more information the operators are required to record, the more opportunity there is for error.

One approach is to go right back to the beginning and ask the following questions:

·        What information is required by regulations?  For example, 21CFR211.186 requires a complete list of components in the master production record.

·        What additional information is required to enable the operators to make decisions?  For example, specify the acceptable range for a processing parameter so that the operator can take appropriate action if the limit is approached.

·        What is the sequence of events?  This is one danger area - the point at which too much information can be supplied.  So ask yourself: what experience do the operators have?  What can be covered by training and what absolutely has to go in the manufacturing instructions?  If you have a high staff turnover you will need to include more information than if you have a group of very experienced operators.

·        What information can be provided elsewhere?  Another danger area - don’t fall into the trap of pulling out a lot of information into SOPs - there are other options (see below).

·        What do regulations require you to record?  Which steps require second-person checks?  (This will depend on the stage in production of the product.  For example, API finished products require greater control than early-stage isolated intermediates.)

·        What additional information do you need to record to ensure the process runs smoothly?  A regulatory parameter recorded later in the process may be heavily dependent on a non-regulatory parameter earlier on, so you would record the earlier parameter too.

·        Is there additional information you need to record for traceability in the event of a deviation?

Now remove everything else.

Poor format for data recording

It must be absolutely clear to your operators what they need to record and in what format.  It also needs to be obvious, both to them and to QA reviewers, what information is missing.  Yet I have seen batch records in which a parameter was recorded in a small underlined space in a few lines of text -- very easily overlooked.  The format for recording other information was inconsistent: this is likely to confuse an operator if different layouts are used for the same type of information.

Guidelines for data recording will be provided in a future Field Report.

Poor control system

Version control is vital, but you don’t want to spend huge amounts of time managing the documents either.  You can map and analyse your review/update/issue system as described in an earlier Field Report: these are the essential points to consider:

·        Do you update your document every time a change is needed, or do you ‘collect’ changes over a period and make the changes all at once?  Regulations allow a certain amount of red-lining.  Is there always a rationale behind the changes?

·        Are the documents always reviewed by the same departments, or just those whom the change impacts?  For example, a change made for a purely GMP reason is unlikely to need reviewing by the Safety department.

·        Who makes the changes, and how are the versions managed?  Is there any opportunity for mix-ups?

·        How is document issue and recall controlled?

Obviously getting things wrong has a negative impact on the business, but let’s flip this round and instead consider how getting it right can have a positive impact.

·        If you’ve got it right, updating and issuing MPIs requires fewer man-hours to achieve.

·        Operators make fewer errors, and those that they do make are easier to spot.

·        Reviewing MPRs is no longer the rate-limiting step for batch release.