Product Dossier
Product Dossier: Zinc Oxide Pharma EP-grade
CONTENT
- Regulatory information and statements
- Product information
- Composition
- Manufacturing flow
- Origin and Naturality
- Statements
- Impurities (chemicals, heavy metals and nitrosamines)
- Registrations
- Quality certificates
REGULATORY INFORMATION AND STATEMENTS
1. Product information:
1.1 Appearance
White powder
1.2 Retest date
18 months
1.3 Storage information
Retest date is valid if stored either
- • in a four layer bag (paper/paper/polyethylene/paper) or,
- • in a polypropylene bag or in a triple layer paper bag placed in a polyethylene bag or,
- • in a four layer bag (polyethylene terephthalate/ aluminium/ polyamide/polyethylene).
Keep in closed container, out of humidity and sun/light exposure.
1.4 Tariff Code
28.17.0000
1.5 Country of Origin
The Netherlands
1.6 Manufacturing site
EverZinc Nederland BV
Muggenweg 2
6245 AB Eijsden
The Netherlands
2. Composition break-down
| Constituent | CAS | EINECS | Nominal content |
| Zinc oxide | 1314-13-2 | 215-222-5 | 100 %wt |
3. Manufacturing flow
Zinc oxide Pharma EP-grade is manufactured from high purity zinc metal - SHG (100% from mineral origin).
The manufacturing process for Zinc oxide Pharma EP-grade includes thermal treatment after which the materials are packed.
There are no catalyst used, no additive added and there are no purification or sterilization (irradiation) steps involved.
The manufacturing process is further free of solvents.
Zinc oxide Pharma EP-grade is manufactured and tested in compliance with GMP Part II / ICH Q7 requirements.
Process flow description:
4. Origin and Naturality
4.1 Origin:
Mineral
4.2 Natural index: (ISO 16128-1:2016 and ISO 16128-2:2017)| Product | Natural Index | Natural Origin Index |
| Zinc oxide Pharma EP-grade | 0 | 1 |
4.3 COSMOS
Compliant
5. Statements
| Allergens | Regulation (EC) n°1223/2009 as amended: Zinc oxide Pharma EP-grade is free of allergens. Moreover, based on our best knowledge, it is further free of additional allergens like glutamate, corn, maize, cocoa, chicken meat, beef, pork, legumes, carrots. |
| Gluten | This raw material is, based on best of our knowledge, free of gluten. |
| Preservative | This raw material is free of preservative. |
| Substances Prohibited | This raw material does not contain any of the substances listed in Annex II ('List of substances prohibited in cosmetic products') of the European Commission's Cosmetic Ingredient Database (CosIng). |
| GMO | Zinc oxide Pharma EP-grade does not contain and/or is manufactured from Genetic Manipulated Organisms (GMO). |
| BSE/TSE | Zinc oxide Pharma EP-grade is free of animal derived ingredients. As a result, Zinc oxide Pharma EP-grade is free of Transmissible Spongiform Encephalopathy (TSE), including Bovine Spongiform Encephalopathy (BSE). |
| VOC | Zinc oxide Pharma EP-grade is free of Volatile Organic Compounds. |
| Residual Solvent | (Ref. Q3C(R8)) Zinc oxide Pharma EP-grade is produced with a process free of solvent. Zinc oxide Pharma EP-grade is consequently free of residual solvents. |
| SVHC | Zinc oxide Pharma EP-grade does not contain any Substances of Very High Concern (SVHC) as listed on the ECHA Website in the “Candidate List of Substances of Very High Concern for authorisation”, last up-dated 17th of January 2022, in a concentration above 0.1%. |
| Heavy Metals | Monitoring of heavy metals is carried out on a regular basis. If present, trace heavy metal levels in Zinc oxide Pharma EP-grade will be well within the limits of the European (EP) pharmacopoeia. |
| Halal | Zinc Oxide Pharma EP-grade: - Does not contain nor come into contact with animal derived materials during manufacture and storage. - Does not contain nor come into contact with alcohol and/or alcohol derived materials during manufacture and storage. - Zinc Oxide Pharma EP-grade is manufactured and tested in compliance with GMP Part II / ICH Q7 requirements Therefore, infringement of Islamic food laws is, based on our best knowledge and quality standards, excluded. An official certificate to this effect is not available. |
| Kosher | This raw material is not derived from, nor does it contain pork and/or pork derivatives. Therefore, infringement of Jewish food laws is, based on our best knowledge, excluded. An official certificate to this effect is not available. |
| Vegan | This raw material is free of animal* origin and no animal* product, by-product or derivative are used within manufacturing process (e.g. additives, carrier substances, auxiliary materials like e.g. nutrient media used for fermented-based ingredients) * The term animal refers to the entire animal kingdom, that is all vertebrates and all multicellular invertebrates. Zinc oxide Pharma EP-grade is consequently compliant with vegan standards. |
| Conflict Minerals | Zinc oxide Pharma EP-grade is used free of Conflict Minerals as defined by the Dodd-Frank Act (e.g. gold, tin, tantalum, and tungsten emanating from the Democratic Republic of Congo (DRC) and adjoining countries (DRC countries)). |
| Impurities | The presence of any impurities is non-intended and technically unavoidable in good manufacturing practice. |
6. Impurities
6.1 Chemicals impurities
Based on best of our knowledge, Zinc oxide Pharma EP-grade is free of the following chemicals / impurities:
Polyacrylic Aromatic Hydrocarbons
Paraben
Petrolatum
Phosphate
Silicone
Latex
Phthalates
Pesticides
Formaldehyde
1,4-Dioxane
Ethylene Oxide
Sulfates
Oxybenzone
PABA (para-aminobenzoic acid)
Monomers
Amines
Sugars (sucrose, glucose/dextrose, fructose, lactose, galactose, maltose, starch)
Sodium
Ethanol
6.2 Heavy Metals – Impurity profile
Reference: ICHQ3D guidance
It is confirmed that risk management evaluation in line with the ICHQ3D guidance was performed on Zinc oxide Pharma EP-grade and is summarized below. Assessment was performed on (at least) the elements from class 1 and 2A from 6 process validation batches (1 ton batch – 99 samples) and measured by ICP.
There are all trace impurities non-intentionally added and technically unavoidable under good manufacturing practice (GMP). This low level of impurities are mostly coming from the raw material used for the manufacturing of the Zinc Oxide Pharma-EP grade.
|
Element |
Class |
Intentionally added |
considered in risk managment |
conclusion |
|
Cd |
I |
no |
yes |
≤ 5 ppm *1 |
|
Pb |
I |
no |
yes |
≤ 10 ppm *1 |
|
As |
I |
no |
yes |
≤ 1 ppm |
|
Hg |
I |
no |
yes |
≤ 1 ppm |
|
Co |
2A |
no |
yes |
≤ 1 ppm |
|
V |
2A |
no |
yes |
≤ 1 ppm |
|
Ni |
2A |
no |
yes |
≤ 1 ppm |
|
Tl |
2B |
no |
yes |
≤ 5 ppm *1 |
|
Au |
2B |
no |
no |
- |
|
Pd |
2B |
no |
no |
- |
|
Ir |
2B |
no |
no |
- |
|
Os |
2B |
no |
no |
- |
|
Rh |
2B |
no |
no |
- |
|
Ru |
2B |
no |
no |
- |
|
Se |
2B |
no |
yes |
≤ 1 ppm |
|
Ag |
2B |
no |
no |
- |
|
Pt |
2B |
no |
no |
- |
|
Li |
3 |
no |
no |
- |
|
Sb |
3 |
no |
no |
- |
|
Ba |
3 |
no |
no |
- |
|
Mo |
3 |
no |
no |
- |
|
Cu |
3 |
no |
yes |
≤ 1 ppm |
|
Sn |
3 |
no |
no |
- |
|
Cr |
3 |
no |
yes |
≤ 1 ppm |
*1 is de specification of EP 10.6 Monograph 0252
6.3 Nitrosamines
Reference : MAHs of all human medicinal products containing chemically synthesized active pharmaceutical ingredients (APIs) should work with the manufacturers of their APIs and finished products in order to evaluate the risk of nitrosamines being present in their products, and take appropriate risk mitigating measures. The evaluations are necessary in light of the detection of nitrosamines in some sartan medicines and the subsequent Article 31 referral which concluded in April 2019, as well as phase 1 of CHMP’s review under Article 5 (3) of Regulation (EC) No. 726/2004 of the presence of nitrosamine impurities in human medicinal products containing chemically synthesized active pharmaceutical ingredients.
Nitrosamines are chemical compound of the chemical structure R1N(–R2)–N=O, a nitroso group bonded to an amine, typically originated from the reaction of nitrites chemical type with secondary or tertiary amines.
EverZinc Nederland BV as manufacturer of Active Pharmaceutical Ingredient Zinc Oxide did consider the following risks to asset potential nitrosamines forming:
- • Is there a risk of nitrosamines forming in the API synthetic process taking into consideration the combination of reagents, solvents, catalysts and starting materials used, intermediates formed, impurities and degradants?
- • Is there a potential risk of nitrosamine contamination (e.g. from recovered materials such as solvents, reagents and catalysts, equipment, degradation, starting materials or intermediates)?
- • Is there any potential of nitrosamine formation during the manufacture of the finished product and/or during storage throughout its shelf life?
Risk assessment conclusion:
Risk is very low to inexistent in potential formation of Nitrosamines during the manufacturing process and shelf life of the EverZinc’s API Zinc Oxide.
Review of the risk assessment is limited to on-site audit.
REGISTRATION
| REACH | ||
| Zinc oxide Pharma EP-grade (as 100 % zinc oxide) is registered and compliant with current Reach regulations. As European manufacturer of the zinc oxide (EINEC number 215-222-5), the registration reference for EverZinc Nederland B.V. is 01-2119463881-32-0016. |
||
| FDA | ||
| EverZinc Nederland B.V is registered as drug establishment with F.E.I number: 3004732851. Zinc oxide Pharma EP-grade is compliant for OTC products on US market. NDC code: 80723-200 |
||
| EUROPE (API manufacturing site) | ||
| EverZinc Nederland B.V is registered as manufacturer of Active Substances to be used as starting materials in medicinal products for human use. API registration number: 5738 API. |
||
| CEP (Certificate of European Pharmacopeia suitability) | ||
| EverZinc Nederland B.V. is the holder of the certificate of suitability CEP reference: R1-CEP2012-347-Rev 00 for Zinc oxide in currently under EDQM revision next to CEP adaptation in line with EP 10:6 requirements. |
||
QUALITY CERTIFICATES
- ISO 9001:2015 (expired in Dec.2024) with approval number ISO 9001-0016497
- ISO 14001:2015 (expired in Dec. 2022) with approval number ISO 14001-0016496
- GMP (Good Manufacturing Practices) delivered by the Heath and Youth Care Inspectorate – Pharmaceutical product with certificate number: NL/API21/2030695 (issued on 27/07/2021).