SOP on Handling Nomor dokumen : 01

Out of Edisi/Revisi : 01

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Judul : SOP on Handling of Out of Specification Results in quality control

Tujuan :

 Sebagai acuan bagi pihak pihak terkait yang akan handling data out of
specification
 SOP ini dibuat untuk memberikan pelayanan kepada peneliti atau jasa pemakai
jasa (pelanggan)

Ruang lingkup :

 Kegiatan di laboratorium uji, PT. Y Laboratory dalam hal handling data yang out
of specification

Acuan :
 Pharma Editoron: December 12, 2016In: QA & QC, Quality Assurance, SOP

SOP Handling Data Yang Out of Specification

 OBJECTIVE

To lay down a procedure for handling of Out-of-Specification (O.O.S.) test

results generated during the testing.

 SCOPE

These procedures are applicable to all QC testing of raw materials, finished

product, and stability samples.

 RESPONSIBILITY

Analyst/ Quality Assurance Manager

 ACCOUNTABILITY

Quality Assurance Manager

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 PROCEDURE

All out-of-specification test results (i.e. suspected test results that fall outside the
established specifications or acceptance criteria) shall be investigated.

When an Out-Of-Specification test result is generated/ suspected, the analyst shall

inform to the QA Manager immediately about the test results.

OOS number shall be allocated in the following manner. OOS/YY/XXX, where

OOS represent the Out of specification, YY indicates the last two digits of the
year & XXX indicates the serial number from 001 to 999. Enter the details in Log
Book for out of specification results as per Annexure –I.

QA Manager will assess the data based on investigation to ascertain if the results
can be attributed to laboratory error, or whether the results indicate problems in
the manufacturing process.

Accordingly, the investigation Phase I and/ or II (Phase-I and II investigation

relates to laboratory error and investigation of problems in manufacturing
process, respectively) will be decided.

Phase-I Investigation

Both analyst and QA Manager are responsible for completing the Phase-I
investigation (Annexure-II).

The first part of this investigation shall be an initial assessment of the accuracy of
laboratory’s data (i.e. finding of an assignable cause, as per Annexure-I), before
any test solutions are discarded.

Re-testing on the retained test solutions/ standard solutions shall be performed

immediately by the same analyst who performed the original test, (For this
purpose, all original test solutions shall be preserved until calculation of test
results is done).

If clear evidence of laboratory error exists and the cause of OOS can be assigned
to this laboratory error (like sample preparation, analytical method followed,
equipment malfunctions etc.) In this case the original O.O.S result may be
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invalidated. The cause of OOS shall be documented, and the subject batch may be
released.

If the initial O.O.S. results are not assigned to original solutions of test
preparations, analyst error, equipment malfunction etc., retest from the original
portions of sample drawn may be performed after due authorization by QA
Manager. Re-testing shall be done (in triplicate) by the analyst other than the one
who has performed original test.

If none of the three results obtained is out of specification, results may be

averaged. The RSD of the triplicate results should not be more than 3%.

If such retest results meet the specifications, cause of original O.O.S. must be
investigated and documented. If the cause can be assigned to a definite Analytical
error with specificity to certain area of retesting, and the O.O.S. is not related to
manufacturing process, then original O.O.S. may be invalidated.

Depending upon the nature of Analytical error, a review shall be performed, if

such errors have past history. Accordingly, review of Analytical method,
equipment calibration or re-training / revalidation of Analyst shall be performed.

Complete review of this investigation shall be documented, to minimize

reoccurrence of such incidents in future.

Re-sampling may be permitted, by Manger-QA, only if, retest data from same
original portion of the sample have been evaluated and the subsequent
investigation gives possible evidence in respect of errors in sampling. (e.g. Non-
representative ness of the original sample is indicated by wide variation in results
from several aliquots of the original sample).

Re-sampling, if permitted, shall be performed using the same sampling

procedure.

Evaluation of data from re-sampled material shall be performed to determine if

original sample was not representative. If there is adequate evidence to support
error in initial sampling (like contamination from sampling tool or wrong
identification or sampling from damaged container etc.), and if it is established
that original O.O.S. result was due to faulty sampling or errors in sampling
procedure, then only the original O.O.S. result can be invalidated.
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Testing of re-sampled aliquot shall be performed by the same analyst who

performed the original analysis and with the same sampling method, in triplicate
to establish new basis for batch release.

If 3 such data meets specifications individually and RSD of data is within 3%

limit, original O.O.S. result is invalidated, and batch may be considered for
release. While taking such decision, it should adequately be established that there
are no failures in Manufacturing Process.

If out-of-specification test results are generated in Disintegration, Dissolution,

and Uniformity of dosage units tests, and the cause is non-assignable, then
applicable Pharmacopoeia (USP/BP/EP/IP) procedure shall be followed.

All steps leading to O.O.S. investigations shall be documented and review of each
failure shall be correlated to occurrence of similar failures in the past. An action
plan shall then be prepared, depending upon the nature of failure found which
caused O.O.S.

If no assignable cause is found till this stage, the original results shall be
considered VALID and the subject batch shall be REJECTED.

For further detailed investigation into O.O.S. result, Phase II investigation shall
be initiated to determine the cause of Failure in the manufacturing process.

Phase – II Investigation

It should be carried by a Group consisting of, Manager QA, Manager Production

and Manager Pharma Technology & Development (PTD) (If required).
(Annexure – II)

This phase shall also take into account the complete evaluation of Batch Process
Records related to the subject batch.

It shall cover complete review/ evaluation into potential manufacturing causes of

the O.O.S result and it’s impact on preceding or succeeding batches of this
product.

Trend analysis of previous batches shall be reviewed, if there is any evidence to

indicate Failures prior to observation of O.O.S. result and also to assess the
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impact of Failure on previous batches. (Phase II investigation may also be

performed parallel to Phase I investigation)

Investigation and resolution of all O.O.S. test results is a priority matter and
hence Phase-I investigation should be completed within 72 hours. In case of a
confirmed O.O.S. Result, Phase II investigation to identify the cause of Failure
should be completed within 30 days and an Action Plan (to prevent the re-
occurrence of the similar test results) should be circulated to all concerned
departments.

Forms and Records (Annexures)

OOS log book – Annexure-I

Phase –I & II investigation report – Annexure-II

Distribution

Master copy – Quality Assurance

Controlled copies- Quality Assurance, Production, Quality Control.engineering

Inti Dari Cara Handling Data Yang Out Of Specification

Ketika hasil pengujian diluar spesifikasi, analis harus segera member tahu manajer
QA tentang hasil pengujian dengan mengisi log book secara detail. Manajer QA akan
menilai data berdasarkan investigasi untuk memastikan apakah hasilnya dapat
dikaitkan dengan kesalahan laboratorium atau mengindikasikan masalah dalam proses
pembuatan.

Investigasi Fase I

Analis dan manajer QA bertanggung jawab dalam melakukan investigasi fase 1. Ini
memuat penilaian awal dari keakuratan data laboratorium, OOS harus
didokumentasikan dan dicatat. Apabila ada kesalahan dilakukan pengujian ulang. Dari
beberapa hasil pengujian tersebut di dirata rata. RSD dari hasil rangkap tiga tidak
boleh lebih dari 3%
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Meninjau metode analisis, kalibrasi peralatan atau pelatihan / revalidasi analis harus
dilakukan tinjauan lengkap untuk meminimalisasikan kesalahan pengujian berikutnya.

Investigasi Fase II

Hasil tes adalah masalah prioritas maka investigasi tahap 1 diselesaikan dalam waktu
72 jam. Hasil OOS yang dikonfirmasi, dan investigasi tahap 2 untuk mengidentifikasi
penyebab kegagalan dan rencana tindakan untuk mencegah terulangnya hasil tes yang
serupa harus diedarkan ke semua departemen yang disetujui.

Nama : Yola Yunita

NIM : 1830240

Kelas : 2F / PLI

Tugas Individu JMA