GOOD DOCUMENTATION PRACTICES

Good documentation practice GDP is a systematic procedure of preparation, reviewing, approving, issuing, recording, storing and archival of any document.

THE IMPORTANCE OF DOCUMENTATION:

As per GMP "If it is not written down, then it did not happen". The document provides information on when, where, who, why and how to complete the task. The document provides evidence proving that the tasks have been completed as they should be.

BASIC REQUIREMENTS OF GDP:

1. Always record the entries at the time of activity simultaneously.

2. Always record date with signature in GMP records.

3. Always use an indelible ballpoint pen to record data in GMP records.

4. Always enter the data directly in the GMP records in the English language.

5. Never use a pencil or erasable or water-soluble ink pen to complete the GMP records.

6. Never use white ink or correction fluid to correct the entry in GMP records

7. Never sign for someone else on any document. Only sign for the work that you have performed yourself.

8. Never back date GMP records.

9. Never discard original raw data of any kind.

10. Never use scratch papers, loose papers or “post it” to record the data.

11. Never discard or destroy any GMP record unless retention period expiry is reached.

12. Documentation and records used throughout the manufacturing process, as well as supporting

processes, must meet the basic requirement of GDP.

List of such documents is provided below (List is not limited):

Batch records

Bill of Materials

Specifications

SOPs

Protocols

Test methods

Checklists

Forms / Log sheets

Training assessments

Certificate of Analysis

Technology transfer document

Validation documents

Maintenance records

Calibration records

GENERAL REQUIREMENTS

Below mentioned requirements should be applied to all the documentation within the GMP environment.

A. Clearly written documentation:

● All documents must be accurate and written in a manner that prevents errors and ensures consistency. 

● If documents are to be used together, e.g. a SOP and a form, then each should reference the other. 

● Ensure there is traceability between two or more documents/records using formal document numbers or record identification. 

B. Using indelible ink:

● All records must be filled out in indelible BLACK or BLUE ballpoint pen for long term legibility. 

● Do not use pencil or ink that can be erased.

C. Legible handwritten Entries:

● A document is unusable if it cannot be read, so care must be taken to ensure that handwriting is legible. All entries must be made at the time the tasks are performed and should be legibly signed and dated. 

● The same is true for electronic documents and records – language should be clear and unambiguous. 

D. Reviewing and approving:

● To ensure that the information is correct and accurate, documents and records should be reviewed by someone who has performed the task and has proper knowledge. A signature and date by the reviewer/approver confirm that a review has taken place. 

● Unsigned documents or records are incomplete and should not be used to perform any task or considered as evidence of a completed task

E. Employee signatures:

● Handwritten signatures must be unique to the individual and listed within the signature register to ensure that the signature is traceable to the concerned employee (or contractor).

● Any employee should not be permitted to sign for another member of staff unless delegated. Signatures must never be forged.

● The management of the signature record should be governed by a procedure and routinely reviewed so that it remains current – new employee should sign the signature register during induction, the signature register must indicate the date employee exit.

PREPARATION OF DOCUMENTS

1. Clear and concise titles should be used for headings, tables, graphs, etc.

2. Pages in the master document should be numbered as X of Y.

3. Full-text spelling with the abbreviation in brackets should be used for the first time. The abbreviation may be used in place of full-text spelling in the remainder of the document.

4. All documents should have the signature and date of the person who prepared the document, reviewed the document and approved the document.

5. All master documents should have an effective date, approval date, and current version number.

6. Respective SOPs should be followed while preparing the documents.

7. Words that everyone can understand should be used. Unfamiliar words reduce the reader’s understanding of what is written. Definitions of abbreviations should always be included in the document for reference. This is most effectively done by including the definitions in a table format, at the start or end of the document.

8. Ensure that the contents of the document are not squeezed into a smaller area just to limit page numbers. Documents with small margins and no spaces between paragraphs and headings can be difficult to look at, hard and slower to read. Space the contents out so that the type/font is easy to read for all users.

9. When creating a document, consider the context in which the document may be used in the future and whether the reader has enough background information.

10 People remember information best when there is a strong visual prompt, such as a diagram. When the document has to be lengthy, consider using tables to structure the information for the easy understanding of the reader.

11. Training of the document should be planned only after approval of document and shall be completed before the effective date.

ISSUANCE AND RETRIEVAL OF GMP RECORDS

1. All the forms associated with the activity should be part of respective SOPs.

2. QA maintains the list of GMP impacting forms and its associated SOP.

3. Records for issuance and retrieval of such forms should be maintained.

RECORDING THE TIME AND DATE IN GMP RECORDS

1. Time should be entered in 24:00-hour cycle. Record the time in HH: MM format. For Example 11:05 AM should be written as 11:05 and 11:05 PM should be written as 23:05.

2. The date should be entered in DD.MM.YY format. For example, 27th July 2013 should be written as 27.07.13.Place “0” before the digit if the digit is less than 10 for the recording of date.

DATA RECORDING IN THE GMP RECORDS

1. Date and time should be recorded in GMP records as mentioned above.

2. Data should be recorded only in the format duly issued and approved by Quality Assurance.

3. Entries in the logbooks should be made in chronological order. Entries should never be pre-completed.

4. Data recording should be done by trained and authorized person.

5. Data should be recorded as it is displayed on the respective equipment panel.

6. Unusual observation during the activity should be recorded, signed and dated. Same should be reported to area person in-charge and QA.

7. If any observation/signature/date are to be repeated, the same should be rewritten. Ditto (----“---) marking or “as above” or “do” should not be used.

8. Manual entries should be reviewed and signed by the second person for accuracy and completeness.

9. Raw data/print outs generated during the activity should be signed at the left bottom with date and should be attached to relevant records. Printouts made on the thermal paper should be photocopied. Thermal paper copy along with photocopy should be attached to the concerned record.

CORRECTION OF ENTRY IN GMP RECORDS

1. Incorrect entries in GMP records should not be overwritten or blocked to make it unreadable.

Always use a single strike out line (For example: Incorrect Entry) to mark the incorrect entry in such a manner that entry remains readable.

2. Correct entry should be written near to the strikeout entry. Person correcting the entry should put the initial signature and date along with corrected entry. Only the person who made the original entry and strikethrough should make the correction. If this is not possible, notify to QA.

3. The reason for correcting the entry should also be documented on the record. In the case of space constraint in the document, the reason for correction should be mentioned on the footer of the record with (*) sign.

HANDLING OF MISSING ENTRY IN GMP RECORDS

1. Entries in the GMP records should be done contemporaneously with the activity. However, the procedure mentioned below should be followed in the exceptional case of missing entry in GMP records.

2. Missing entry in the GMP records can be re-entered later if the data are retrievable. (For example: start time of blender is missed by the operator, however, the entry for the same is mentioned in the equipment usage log)

3. In such case, an entry should be made with a clear indication of the date when the activity was performed and the date the activity is recorded on the document.

4. Document the explanation to substantiate the entry and the reason for the delay in recording.

5. Missing entry in the GMP records for non-retrieval data should be handled through event investigation procedure (For example, operator missed the reading of drying temperature during the operation, where there is no automatic data recording mechanism in place).

WORKING WITH BLANK OR UNUSED SPACE

Blank/Unused space in the GMP records should be strikeout as below with single line with sign and date to ensure that record cannot be added to a later date.

CANCELLATION OF GMP RECORDS

Cancellation of GMP records should only be allowed in the rare case with the approval of QA and in exceptional cases such as spillage of chemical on the record. Event investigation procedure should be followed to determine further course of action. The reason for cancellation should be documented for cancellation of the document and signed by area person in-charge and QA.

SOP for return of Raw & Packing materials from production department.

 1.0 OBJECTIVE:

       To lay down a procedure for return of Raw material &Packing materials from production department.

2.0 SCOPE:

        This SOP shall be applicable for return of Raw & Packing materials from production department.

3.0 RESPONSIBILITY:

        Stores Officer/Assistant

4.0 ACCOUNTABILITY:

       HOD Stores

5.0 PROCEDURE:

5.1 Raw & Packing materials shall be returned  from Production Department to Stores Department only in the following cases:

• Change in production plan.

• Requirement of alternate AR No. / Replacement of issued material.

• Balance Quantities after completion of Batch in case of Packing Material.

5.2 Production person shall fill “ Shop floor internal return note” with all   necessary details along with justification by Production Officer with the duly approved by Quality Assurance person.

5.3 Production person shall ensure that proper identification label is affixed on each pack of the returned quantity of material before transferring the material to Raw and Packing material stores.

5.4  On receipt of the material, store persons shall check the details viz. Item, Item Code, Quantity and A. R. Number of each material as per “Shop floor internal return note”.

5.5  Store person shall keep the materials at their designated place along with respective A.R. No. inventory.

5.6  Store person shall enter the details of returned materials in Bin Cards.

6.0 ABBERIVATIONS:

6.1  SOP - Standard operating procedure

6.2  HOD – Head of Department

Vacancy at Sun Pharma, Gujrat

Vacancy in Sun Pharma, the leading pharma API and Bulk formulation company across the globe,
at Panoli, Ankleshwar, Gujrat, India for the post of officer and Sr. officer in Quality Control , Quality Assurance and Production departments

 the interested candidates can send their updated resume to vashal.joshi@sunpharma.com

INTRODUCTION AND BASICS OF UV SPECTROSCOPY

INTRODUCTION AND BASICS OF UV SPECTROSCOPY

UV spectroscopy is type of absorption spectroscopy in which light of ultra-violet region (200-400 nm.) is absorbed by the molecule. Absorption of the ultra-violet radiations results in the excitation of the electrons from the ground state to higher energy state. The energy of the ultra-violet radiation that are absorbed is equal to the energy difference between the ground state and higher energy states (deltaE = hf).

Generally, the most favoured transition is from the highest occupied molecular orbital (HOMO) to lowest unoccupied molecular orbital (LUMO). For most of the molecules, the lowest energy occupied molecular orbital’s are s orbital, which correspond to sigma bonds. The p orbitals are at somewhat higher energy levels, the orbital’s (nonbonding orbitals) with unshared paired of electrons lie at higher energy levels. The unoccupied or anti-bonding orbitals (pie* and sigma*) are the highest energy occupied orbitals.

In all the compounds (other than alkanes), the electrons undergo various transitions. Some of the important transitions with increasing energies are: nonbonding to pie*, nonbonding to sigma*, pie to pie*, sigma to pie* and sigma to sigma*.

PRINCIPLE OF UV SPECTROSCOPY

UV spectroscopy obeys the Beer-Lambert law, which states that: when a beam of monochromatic light is passed through a solution of an absorbing substance, the rate of decrease of intensity of radiation with thickness of the absorbing solution is proportional to the incident radiation as well as the concentration of the solution.

The expression of Beer-Lambert law is-

A = log (I0/I) = Ecl

Where, A = absorbance

I0 = intensity of light incident upon sample cell

I = intensity of light leaving sample cell

C = molar concentration of solute

L = length of sample cell (cm.)

E = molar absorptivity

From the Beer-Lambert law it is clear that greater the number of molecules capable of absorbing light of a given wavelength, the greater the extent of light absorption. This is the basic principle of UV spectroscopy.

INSTRUMENTATION AND WORKING OF UV SPECTROSCOPY

UV spectrometers consist of the following parts-

1.       Light Source- Tungsten filament lamps and Hydrogen-Deuterium lamps are most widely used and suitable light source as they cover the whole UV region. Tungsten filament lamps are rich in red radiations; more specifically they emit the radiations of 375 nm, while the intensity of Hydrogen-Deuterium lamps falls below 375 nm.

2.       Monochromator-  Monochromators generally composed of prisms and slits. The most of the spectrophotometers are double beam spectrophotometers. The radiation emitted from the primary source is dispersed with the help of rotating prisms. The various wavelengths of the light source which are separated by the prism are then selected by the slits such the rotation of the prism results in a series of continuously increasing wavelength to pass through the slits for recording purpose. The beam selected by the slit is monochromatic and further divided into two beams with the help of another prism.

3.       Sample and reference cells- One of the two divided beams is passed through the sample solution and second beam is passé through the reference solution. Both sample and reference solution are contained in the cells. These cells are made of either silica or quartz. Glass can't be used for the cells as it also absorbs light in the UV region.

4.       Detector- Generally two photocells serve the purpose of detector in UV spectroscopy. One of the photocell receives the beam from sample cell and second detector receives the beam from the reference. The intensity of the radiation from the reference cell is stronger than the beam of sample cell. This results in the generation of pulsating or alternating currents in the photocells.

5.       Amplifier- The alternating current generated in the photocells is transferred to the amplifier. The amplifier is coupled to a small servometer. Generally current generated in the photocells is of very low intensity, the main purpose of amplifier is to amplify the signals many times so we can get clear and recordable signals.

6.       Recording devices- Most of the time amplifier is coupled to a pen recorder which is connected to the computer. Computer stores all the data generated and produces the spectrum of the desired compound.

CONCEPT OF CHROMOPHORE AND AUXOCHROME IN THE UV SPECTROSCOPY

Chromophore- Chromophore is defined as any isolated covalently bonded group that shows a characteristic absorption in the ultraviolet or visible region (200-800 nm). Chromophores can be divided into two groups-

a) Chromophores which contain p electrons and which undergo pie to pie* transitions. Ethylenes and acetylenes are the example of such chromophores.

b) Chromophores which contain both p and nonbonding electrons. They undergo two types of transitions; pie to pie* and nonbonding to pie*. Carbonyl, nitriles, azo compounds, nitro compounds etc. are the example of such chromophores.

Auxochromes- An auxochrome can be defined as any group which does not itself act as a chromophore but whose presence brings about a shift of the absorption band towards the longer wavelength of the spectrum. –OH,-OR,-NH2,-NHR, -SH etc. are the examples of auxochromic groups.

ABSORPTION AND INTENSITY SHIFTS IN THE UV SPECTROSCOPY

There are four types of shifts observed in the UV spectroscopy-

a) Bathochromic effect- This type of shift is also known as red shift. Bathochromic shift is an effect by virtue of which the absorption maximum is shifted towards the longer wavelength due to the presence of an auxochrome or change in solvents.

The nonbonding to pie* transition of carbonyl compounds observes bathochromic or red shift.

b) Hypsochromic shift- This effect is also known as blue shift. Hypsochromic shift is an effect by virtue of which absorption maximum is shifted towards the shorter wavelength. Generally it is caused due to the removal of conjugation or by changing the polarity of the solvents.

c) Hyperchromic effect- Hyperchromic shift is an effect by virtue of which absorption maximum increases. The introduction of an auxochrome in the compound generally results in the hyperchromic effect.

d) Hypochromic effect- Hyperchromic effect is defined as the effect by virtue of intensity of absorption maximum decreases. Hyperchromic effect occurs due to the distortion of the geometry of the molecule with an introduction of new group.

APPLICATIONS OF UV SPECTROSCOPY

1. Detection of functional groups- UV spectroscopy is used to detect the presence or absence of chromophore in the compound. This is technique is not useful for the detection of chromophore in complex compounds. The absence of a band at a particular band can be seen as an evidence for the absence of a particular group. If the spectrum of a compound comes out to be transparent above 200 nm than it confirms the absence of –

a) Conjugation b) A carbonyl group c) Benzene or aromatic compound d) Bromo or iodo atoms.

2. Detection of extent of conjugation- The extent of conjugation in the polyenes can be detected with the help of UV spectroscopy. With the increase in double bonds the absorption shifts towards the longer wavelength. If the double bond is increased by 8 in the polyenes then that polyene appears visible to the human eye as the absorption comes in the visible region.

3. Identification of an unknown compound- An unknown compound can be identified with the help of UV spectroscopy. The spectrum of unknown compound is compared with the spectrum of a reference compound and if both the spectrums coincide then it confirms the identification of the unknown substance.

4. Determination of configurations of geometrical isomers- It is observed that cis-alkenes absorb at different wavelength than the trans-alkenes. The two isomers can be distinguished with each other when one of the isomers has non-coplanar structure due to steric hindrances. The cis-isomer suffers distortion and absorbs at lower wavelength as compared to trans-isomer.

5. Determination of the purity of a substance- Purity of a substance can also be determined with the help of UV spectroscopy. The absorption of the sample solution is compared with the absorption of the reference solution. The intensity of the absorption can be used for the relative calculation of the purity of the sample substance.

FRIBILITY TEST AND APPARATUS

The strength of a tablet plays a very important role in its marketing and dissolution. The mechanical strength of tablet or granules can be determined by its hardness and through friability test.

Measuring the hardness of a tablet is not a reliable indicator for tablet strength as some formulations when compressed into very hard tablets tend to 'cap' or lose their crown portions on attrition. Such tablets tend to powder, chip and fragment. They not only lack elegance and consumer acceptance but also spoil the areas of manufacturing such as coating and packaging. In friability test the tablets are prone to abrasion hence enabling us to check for the tablet strength under application of force in different manner. The friabilator is used for fribility test. most commonly used fribilator is Roche Fribilator.

FRIBILATOR APPARATUS r

Use a drum,^* with an internal diameter between 283 and 291 mm and a depth between 36 and 40 mm, of transparent synthetic polymer with polished internal surfaces, and not subject to static build-up (see figure for a typical apparatus). One side of the drum is removable. The tablets are tumbled at each turn of the drum by a curved projection with an inside radius between 75.5 and 85.5 mm that extends from the middle of the drum to the outer wall. The drum is attached to the horizontal axis of a device that rotates at 25 ±1 rpm. Thus, at each turn the tablets roll or slide and fall onto the drum wall or onto each other.

For tablets with a unit mass equal to or less than 650 mg, take a sample of whole tablets corresponding to 6.5 g. For tablets with a unit mass of more than 650 mg, take a sample of 10 whole tablets. The tablets should be carefully dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets in the drum. Rotate the drum 100 times, and remove the tablets. Remove any loose dust from the tablets as before, and accurately weigh.

Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are present in the tablet sample after tumbling, the sample fails the test. If the results are doubtful or if the weight loss is greater than the targeted value, the test should be repeated twice and the mean of the three tests determined. A maximum mean weight loss from the three samples of not more than 1.0% is considered acceptable for most products.

If tablet size or shape causes irregular tumbling, adjust the drum base so that the base forms an angle of about 10 with the bench top and the tablets no longer bind together when lying next to each other, which prevents them from falling freely.

Effervescent tablets and chewable tablets may have different specifications as far as friability is concerned. In the case of hygroscopic tablets, an appropriate humidity-controlled environment is required for testing.

Drums with dual scooping projections, or an apparatus with more than one drum, for the running of multiple samples at one time, are also permitted.