Delta Training

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VALIDATION What is the point? Alan
Aldcroft Bovis Lend Lease - Pharmaceutical
Division
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• What was the point?

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The Devonport Incident

• Tue 6th April 1971, Evans Medical in Speke.
  Transfusion Unit manufacture 5 Sterile
  Dextrose Solution Lot D1192
• Intravenous Injection therefore required to be
  sterile
• Terminally Sterilised at 115 C for 30 minutes

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Disclaimer

• At that time Evans Medical was a subsiduary of
  Glaxo and was one of the largest manufacturer of
  generic pharmaceuticals in the UK.
• There is still a company trading under the name
  of Evans Medical, however the company as it
  exists today, is in no way related in ownership,
  management, or operations to the Evans Medical
  that existed then.

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Sterilisation of Sterile 5 Dextrose
1.7 Bar
115C
Steam 1.7 Bar
115C
Chart
115C at 1.7 Bar for 30 minutes
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Sterilisation of Batch D1192/C
1.7 Bar
115C
P
115C
Steam 1.7 Bar
47C
47C
Drain
Chart
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The Devonport Incident

• 6th April 1971 Evans Medical manufacture 5 Ster
  Dextrose Sol. Lot D1192/C
• May 1971 Lot D1192/C distributed
• 29th Feb 1972 2 deaths at Devonport Hospital
• 1st Mar 1972 2 further deaths at Devonport
• 2nd Mar 1972 1 further death at Devonport
• 6th Mar 1972 Investigation begins
• 12th Jul 1972 Clothier Report issued.

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Findings of the Clothier Report

• Lack of instrument calibration
• Lack of maintenance activity
• Lack of maintenance logs
• Inadequate procedures
• Lack of procedures
• Inadequate equipment
• No batch record review
• Inadequate equipment cleaning
• Poor staff training

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Effects of the Clothier Report

• Ensure that critical instruments were functional
  and calibrated regularly
• Prove that SOPs were accurate
• Prove that operators had been trained
• Test and prove that the process would work time
  and time again
• Document that this had been done

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FDA Guidelines 1984 Validation

• Establishing DOCUMENTED evidence which provides
  a high degree of assurance that a specific
  process will CONSISTENTLY produce a product
  meeting PRE-DETERMINED specifications and quality
  attributes.

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Do We Have to Validate?
VALIDATION IS SPECIFICALLY REFERRED TO IN THE EC
DIRECTIVES AND IS A BASIC PRINCIPLE OF GOOD
MANUFACTURING PRACTICE (GMP)
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If Pharma Companies ignore GMP?

• Increased attention from regulators
• Products withdrawn from market (Recall)
• Adverse publicity, patient safety concerns
• Loss of confidence by industry peers and
  regulators
• Permission to sell products withheld
• Order to stop manufacture and sale of products
• (In US) prosecution and prison for individuals

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The Benefits Of Validation

• REDUCING
• Rejects
• Reworks
• Reliance on In-Process Controls
• Equipment Downtime

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What is the point?

• Validation saves lives!