OOT Investigation Form in Pharmaceutical Industry

An Out of Trend (OOT) investigation is a critical quality assurance process within the pharmaceutical industry, aimed at ensuring product consistency, safety, and efficacy. OOT refers to test results that exhibit an unexpected deviation from established trends, despite falling within the specified acceptance criteria. These results can indicate potential issues in the manufacturing process, stability of the product, or variations in raw materials and equipment performance.

Key Aspects of OOT Investigation

• OOT results are test results that deviate significantly from historical data trends, even though they are not necessarily out of specification (OOS). This can occur in stability studies, manufacturing processes, or quality control tests.
• An OOT event is typically triggered when a result, though within specification, shows a shift from past data or established trends. For instance, if stability data for a batch of drugs shows a gradual potency loss over time, but one result falls significantly lower than expected at a particular time point, it would be considered OOT.
• Investigating OOT involves performing a detailed root cause analysis. The aim is to determine why the result deviates from the expected trend. This could be due to factors such as:

1. Variability in raw material quality
2. Manufacturing process deviations
3. Analytical method issues
4. Environmental or storage conditions impacting product stability

• Once the cause is identified, a risk assessment is conducted to evaluate the impact on product quality, patient safety, and regulatory compliance. If necessary, corrective actions are implemented, such as changes to the process or further testing.
• If the OOT investigation identifies a specific problem, corrective and preventive actions (CAPA) are implemented to avoid future occurrences. This may involve adjusting the manufacturing process, retraining staff, or improving raw material sourcing.

ALSO READ: SOP for Handling Out of Specification (OOS)

Date of OOT occurrence:

OOT Reference No.:

A] OOT REPORTING: (To be completed by the analyst)

Product / Material Name

QC Reference No.

Batch No.

Mfg. Date

Specification No.

Expiry Date

Test Name

Test Method No.

Stage of testing (For Drug substance / Intermediate / Drug product)

In-process  Finished product / Intermediate release testing  Stability    Months Accelerated / Long Term / Intermediate

Summary of OOT Test Results (state result and specification)

Details of abnormal observations noted during the testing if any

Analyst Name

Signature & Date

B] LABORATORY INVESTIGATION:

Sr. No.

Check Parameters

Observations (Yes/No/NA)

Comments

1

Sampling

Any abnormal observation noted during sampling?

Any noticeable difference in sample appearance?

A sample is correctly collected & labeled?

Sample storage was done appropriately?

2

General

Any unusual happening in lab? (e.g. power failure)

Was the method discussed with the analyst?

The correct analytical method used?

The analyst was trained to perform the test?

Correct glassware used for dilutions?

Glassware were properly cleaned?

Instruments used are qualified?

Instruments used within calibration validity period

Instrument Used (Name & Id)

Calibration Due

Instrument setup & operation as per standard operating procedure?

Use of appropriate grade of chemical and reagents within the validity period?

Correct normality/molarity of volumetric solutions used?

VS used

Valid up to date

Strength

3

Sample / Standards Preparation

Sample & Std preparations done as per the test method?

Is any weighing error identified?

Correct potency of the standard used in the calculation? Standard is within the validity period?

Std(s) Used

Valid up to date

Potency

Is the sample properly shaken, sonicated or heated / warmed as per method of analysis?

Are the sample / standard dilutions correctly performed as per method of analysis?

Any noticeable preparation? Difference noted in the sample/Standard

Are the samples filtered/ centrifuged / membrane filtered properly before introduction into the instrument or analysis by classical method?

Are samples/standards preparations stored under correct environment/time before analysis?

Tablets/granules are ground properly?

Any errors in calculation and transcription?

4

Chromatography

Correct Column Used (E.g. column make, Dimension, Particle Size, End capped / Non-End capped, Pore Size, Carbon Loading)?

Any leakages observed in the fittings?

Correct instrument parameters used (e.g. for HPLC – type of detector, flow rate, oven temp., wavelength, injection volume, sample temp.  For GC – type of detector, flow rate, oven temp. Injection volume, Inj. Temp, detector temp.)?

Mobile phase preparation is as per the method (check for composition, pH, air bubbles)?

Any unusual or unexpected response observed with standard or test preparations?

System suitability acceptance criteria were met during the analysis?

5

Dissolution

Correct instrument parameters used (apparatus type, speed, bath temperature, time, medium used, volume)?

Dissolution Medium Degassed?

Sample Withdrawn Correctly?

Correct Filter Used?

6

Microbiological Assay

Was media from a single prepared lot used in the assay?

Was there any malfunction or breakdown of the incubator?

Was the temperature of the incubator during the incubation period as per requirement?

Are the zones of inhibition/exhibition clearly defined?

Is the merging of zones seen?

Was zone reading done as per SOP?

Is the Zone reader/vernier calipers in the calibrated state?

Instrument ID: Calibration due date:

7

Stability

Any malfunction or breakdown of stability chamber?

Any failure of utilities (power, water, UPS)?

Any deviation in temperature / humidity monitoring?

Any damage to pack?

Any deviation from SOP for sample pull out time?

Were samples, after pull out, stored as per the conditions specified in the SOP?

Were samples analysed within the specified time period as in the SOP?

Any change in method of analysis or specification?

Any other (to be specified)

8

Any other findings (review of method validation data, Trend data etc.):

9

Was similar OOT reported for this product earlier? If yes, state the identified cause and corrective / preventive actions taken that time –

10

LABORATORY ERROR IDENTIFIED : Yes / No

If yes, describe the error:

QC Analyst (Sign & Date)

Section Incharge of QC (Sign & Date)

11

ACTION TO BE FOLLOWED ( In case of lab error)

Yes/No

Comment

Retesting of retained sample solution by Original Analyst

Retesting of retained sample by Original Analyst

Correction in document

Any other (To be specified)

Section In-charge Of QC (Sign & Date):

12

ACTION TO BE FOLLOWED  (In case of obvious error related to sampling or sample handling)

REASON FOR RE-SAMPLING:

RE-SAMPLING PLAN:

Total number of containers

Number of containers to be sampled

Sample quantity from each container

Remarks or Special instructions:

QC In-charge (Sign & date)

QA In-charge (Sign & date)

13

RESULT OF RETEST (in case of obvious lab / sampling error):

1.

2.

Average =

QC Analyst (Sign & Date)

QC In-charge (Sign & Date)

CONCLUSION: OOT test result              Valid, Report the initial result   Invalid, Report new results   If OOT is valid, ÿ Initiation of Manufacturing Investigation

QA In-charge: (Sign & Date)

C]

MANUFACTURING INVESTIGATION:

For details, refer to Annexure 4 - Manufacturing Investigation Form.   Manufacturing Error detected: Yes / No

Production In-charge (Sign & Date)

QA In-charge (Sign & Date)

QA decision on disposition of the batch:           QA In-charge (Sign & Date)

D]

CLOSURE OF OOT INVESTIGATION

Summary and Conclusion: (Based on report of Laboratory / Manufacturing investigations)     Assignable Cause:     Corrective Action and Preventive Action:  If CAPA not completed within 30 days, CAPA ref. no.

QC In-charge (Sign & Date)

Production In-charge (Sign & Date)

QA In-charge (Sign & Date)

List of Attachments (if any):

ALSO READ: SOP for Handling of Out of Trend (OOT)