OOS (Out of Specification) As PER USFDA & MHRA

OOS (Out of Specification)

Definition: It is defined as those results of the in-process or Finished which has been sed products testing, which falling out specified limit or acceptance Criteria which has been specified in the official Monograph or  Product registered  Specification.

OOS was found due to the following reasons:

  1. Laboratory Related OOS
  2. Process Related OOS
  3. Sample Homogeneity OOS

1. Laboratory Related OOS (Testing Error):

  • Method of Analysis
  • Non- Calibrated Instruments Used
  • Calculation Error
  • Analyst Error
  • Instruments Failure

2. Process Related OOS (Manufacturing Error):

  • Operator Error
  • Equipment Error
  • Deviation from Validated Procedure
  • Quality of RM/Intermediates Used
  • In-process Control During Manufacturing

3. Sample Homogeneity OOS (Sampling Error & Handling):

  • Sampling Error
  • Handling of Sample
  • Pooling of Sample

Investigation of OOS As Per USFDA

  1. Phase I Investigation – Laboratory Investigation
  2. Phage II Investigation – Full-Scale Investigation

Phase I Investigation – (Laboratory Investigation)

  • Assessment of Raw Data
  • Calculation
  • Instruments Calibration
  • Reference Standard/Chemical
  • Method Validation
  • Reexamination of  Volumetric/glassware

Phage II Investigation – (Full-Scale Investigation)- It is divided into two parts

Phage II (A) –

  • Production Process Review
  • All Departments Involved In Production

Phage II (B) –

  • Additional Laboratory Testing
  • Retesting
  • Resampling

Investigation of OOS As Per MHRA

  1. Phase I Investigation – Laboratory Investigation
  2. Phage II Investigation – Manufacturing Investigation
  3. Phage III Investigation – Extended  Manufacturing Investigation

Phase I Investigation – Laboratory Investigation:

  • Phase I A: Primary Laboratory Investigation
  • Phase I B: Extended Laboratory Investigation

Phage II Investigation – Manufacturing Investigation:

  • Process Parameter
  • Drying Parameter
  • Input RM Quality
  • Training of Personnel
  • Cleaning of Equipment
  • Environmental Monitoring

Phage III Investigation – Extended  Manufacturing Investigation:

Sampling Error

Authorized for Resampling


If root cause found -Defined the CAPA or If not

Diverted to the Matter R&D, ADL, or PD Lab

Conclusion of All Team Members (QA, QC, Production, R&D, ADL, or PD Lab)

Decided the Fat of Batch by QA Head


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About Pharmaceutical Guidanace

Alice is the Author and founder of pharmaceutical guidance, she is a pharmaceutical professional having more than 18 years of rich experience in pharmaceutical field. During her career, she works in the quality assurance department with multinational companies i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, and Nectar life Science Ltd. During his experience, she faces many regulatorily audits i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda, Kenya, Tanzania, Zimbabwe. She is currently leading a regulatory pharmaceutical company as a Head Quality. You can join him by Email, Facebook, Google+, Twitter, and YouTube

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