InstantGMP Compliance Series for Dietary Supplements

Documentation of cGMP Procedures

Electronic cGMP Manufacturing Execution System2

Background

• Dietary Supplements are orally ingested products that contain an ingredient that is intended to supplement the diet

• Not controlled by the FDA until 2007• By 2010 all manufacturers or distributors of

dietary supplements had to be in compliance with cGMP requirements

• Now 1 in 4 manufacturers inspected by FDA receive Warning Letters

Electronic cGMP Manufacturing Execution System

GMP Problems with Documentation

• Most common citation in FDA Warning Letters – inadequate documentation

• Lack of detail on written procedures• Inadequate control of specifications• Failure to perform review and disposition• Insufficient or non-existent Master Manufacturing

Records• Batch records did not follow the Master• QC did not properly disposition batch

Electronic cGMP Manufacturing Execution System

Why Documentation Is Important

• Impossible to stay in compliance without written documentation

• Used to train quality and operations staff• Assures consistency in how processes are

followed• Enforces uniformity and quality• if adulteration occurs, records will show the

source of the material so that its use can be stopped

Electronic cGMP Manufacturing Execution System

Why FDA is Hot on Documentation

• They want records to show:– What was manufactured– If controls were in place to control quality– What deviations occurred– That corrective actions were effective – If a product should be recalled– That cGMPs were followed

• In the FDA’s mind – “If it wasn’t documented, it wasn’t done”

Electronic cGMP Manufacturing Execution System

Improving Documentation

• First rule of cGMP Compliance: “Document what you do and do what you

document”

• FDA guidances on cGMP have the details• Interpretation is allowed – just write up what

you intend to do as SOPs• Then follow them

Electronic cGMP Manufacturing Execution System

Records Are Required For:

1. Personnel2. Sanitation3. Calibration of instruments and controls 4. Calibration and inspection of automated,

mechanical, or electronic equipment5. Maintaining, cleaning, and sanitizing equipment

and utensils and other contact surfaces6. Water used as a component7. Production and process controls

Electronic cGMP Manufacturing Execution System

Records Are Required For:

8. Quality control9. Components, packaging, labels and product

received for packaging and labeling10. Master manufacturing and batch production11. Laboratory operations12. Manufacturing operations13. Packaging and labeling operations14. Holding and distributing operations15. Returned dietary supplements16. Product complaints

Electronic cGMP Manufacturing Execution System

Most Common FDA Citations

• Inadequate documentation of cGMP procedures • No Master Manufacturing Records created • Batch production records had inadequate information

or didn’t follow the master• No documentation that specifications were set• No in-process control• Deviations occurred without corrective action or

documentation• Suppliers and vendors were not qualified

Electronic cGMP Manufacturing Execution System

Master Manufacturing Records Must Have:

• Complete list of components (Bill of Materials)• Weight or measure of each component • Identity and measure of each dietary ingredient• Theoretical yield at each step where control is needed• Expected yield when manufacturing is completed• Written instructions for each step of the manual

operations• Specifications at each step where control is necessary• Procedures for sampling• Where one person adds components, another person

verifies the addition• An equipment list with proper cleaning checked

Electronic cGMP Manufacturing Execution System

Batch Production Records Must Have:

• Identity of equipment and processing lines used • Date and time of the maintenance and cleaning,

or a cross-reference to logs• Identity and weight or measure of each

component• Actual yield and percent theoretical yield• Documentation that finished dietary supplement

meets specifications

Electronic cGMP Manufacturing Execution System

Batch Production Records Must Have:

• Unique batch number for each batch• Proof that quality control reviewed the BPR and

dispositioned the batch• All results which were obtained during the operation• Reference to the physical location of the label• Manufacturing steps for tablets and capsules to prevent

metal or other foreign materials from equipment getting into the batch

Electronic cGMP Manufacturing Execution System

Specifications Needed For:

• Components• In-process production• Labels and packaging• Finished batch of dietary supplement• Product that you receive from a supplier for

packaging and labeling• Packaging and labeling for the finished dietary

supplement

Electronic cGMP Manufacturing Execution System

In-Process Controls

• Must monitor the steps where control is necessary to ensure quality

• Determine whether the in-process specifications are met

• Controls include COA from qualified vendors• Dietary ingredients need identity testing• Use scientifically valid method for each specification• Quality control personnel must conduct all reviews and

make disposition decisions

Electronic cGMP Manufacturing Execution System

Deviations

• Triggered by any unanticipated occurrence could result in adulteration

• May not reprocess a batch that deviates unless approved by Quality

• Quality must conduct a material review• Then make a disposition decision• Corrective and Preventative Actions (CAPA)

needed for deviations

Electronic cGMP Manufacturing Execution System

Supplier/Vendor Qualification Programs must include:

• A program for periodic audits and re-qualifying of vendors

• Qualification of all suppliers including components, ingredients, labels, etc.

• Confirmation of vendor's test results and certificates of analysis

Electronic cGMP Manufacturing Execution System

Supplier/Vendor Qualification Programs must include:

• Reviews of specifications, procedures, and lab controls

• Assurance that all personnel affected by cGMP are trained

• Regular review of vendor’s documentation• Calibrations and recalibrations performed by

the equipment manufacturer if not done in-house

Electronic cGMP Manufacturing Execution System

How Long Must Records be Kept?

• Length of time product complaints are likely to arise

• Generally 2 years after date of distribution (not date of manufacture)

• If shelf life dating is used, 1 year past the shelf life date

Electronic cGMP Manufacturing Execution System

How Must Records be Kept?

• Records are the backbone of a quality system• FDA must have the means to examine them

during an inspection• If microfilming is used, a suitable reader must

be available• If electronic, must meet 21 CFR Part 11

requirements

Electronic cGMP Manufacturing Execution System

SOPs Made Easy

• InstantGMP maintains a complete set of manufacturing Standard Operating Procedures (SOPs) and Policies for cGMP manufacturing

• Available as individual SOPs to supplement what you already have

• Available as an entire set as a foundation for a complete quality system

www.instantgmp.com/Standard-Operating-Procedures

InstantGMP™

Find more videos on cGMP Compliance for Dietary

Supplements in the Resource Center at

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